Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8
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Also known as MDDGA8muscle-eye-brain-POMGNT2 relatedmuscular dystrophy-dystroglycanopathy, type A caused by mutation in POMGNT2POMGNT2 muscular dystrophy-dystroglycanopathy, type A
Summary
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8 (MONDO:0013904) is a disease caused by POMGNT2 (GenCC Definitive), with 3 cohort genes.
At a glance
- Causal gene: POMGNT2 (GenCC Definitive)
- Cohort genes: 3
- ClinVar variants: 434
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 a, 8 |
| Mondo ID | MONDO:0013904 |
| OMIM | 614830 |
| DOID | DOID:0111231 |
| UMLS | C3553813 |
| MedGen | 766727 |
| GARD | 0015846 |
| Is cancer (heuristic) | no |
Also known as: MDDGA8 · muscle-eye-brain-POMGNT2 related · muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8 · muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies, type A, 8 · muscular dystrophy-dystroglycanopathy, type A caused by mutation in POMGNT2 · POMGNT2 muscular dystrophy-dystroglycanopathy, type A
Data availability: 434 ClinVar variants · 4 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 a, 8
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, 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, muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9
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
434 retrieved; paginated sample, class counts are floors:
223 uncertain significance, 156 likely benign, 20 pathogenic, 16 conflicting classifications of pathogenicity, 9 benign/likely benign, 4 pathogenic/likely pathogenic, 3 likely pathogenic, 3 benign
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 156455 | NM_001101426.4(CRPPA):c.1105GTT[3] (p.Val372del) | CRPPA | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1055376 | NM_032806.6(POMGNT2):c.1326G>A (p.Trp442Ter) | POMGNT2 | Pathogenic | criteria provided, single submitter |
| 1077124 | NM_032806.6(POMGNT2):c.1232_1233del (p.Gln411fs) | POMGNT2 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1252076 | NM_032806.6(POMGNT2):c.503T>C (p.Phe168Ser) | POMGNT2 | Pathogenic | no assertion criteria provided |
| 1376803 | NM_032806.6(POMGNT2):c.509del (p.Asp170fs) | POMGNT2 | Pathogenic | criteria provided, single submitter |
| 1400524 | NM_032806.6(POMGNT2):c.118C>T (p.Arg40Ter) | POMGNT2 | Pathogenic | criteria provided, single submitter |
| 1452812 | NM_032806.6(POMGNT2):c.820_821del (p.Lys274fs) | POMGNT2 | Pathogenic | criteria provided, single submitter |
| 1453141 | NM_032806.6(POMGNT2):c.410_411delinsG (p.Ala137fs) | POMGNT2 | Pathogenic | criteria provided, single submitter |
| 1459409 | NC_000003.11:g.(?43121181)(43122923_?)del | POMGNT2 | Pathogenic | criteria provided, single submitter |
| 1997096 | NM_032806.6(POMGNT2):c.40del (p.Val14fs) | POMGNT2 | Pathogenic | criteria provided, single submitter |
| 2055124 | NM_032806.6(POMGNT2):c.1510del (p.Val504fs) | POMGNT2 | Pathogenic | criteria provided, single submitter |
| 2058172 | NM_032806.6(POMGNT2):c.381_382del (p.Gln128fs) | POMGNT2 | Pathogenic | criteria provided, single submitter |
| 2142831 | NM_032806.6(POMGNT2):c.817_818del (p.Glu273fs) | POMGNT2 | Pathogenic | criteria provided, single submitter |
| 3620611 | NM_032806.6(POMGNT2):c.248G>A (p.Trp83Ter) | POMGNT2 | Pathogenic | criteria provided, single submitter |
| 37207 | NM_032806.6(POMGNT2):c.1333C>T (p.Arg445Ter) | POMGNT2 | Pathogenic | criteria provided, single submitter |
| 436373 | NM_032806.6(POMGNT2):c.745C>T (p.Gln249Ter) | POMGNT2 | Pathogenic | criteria provided, single submitter |
| 4739533 | NM_032806.6(POMGNT2):c.851del (p.Leu284fs) | POMGNT2 | Pathogenic | criteria provided, single submitter |
| 4812128 | NM_032806.6(POMGNT2):c.740_741del (p.Phe247fs) | POMGNT2 | Pathogenic | criteria provided, single submitter |
| 545449 | NM_032806.6(POMGNT2):c.758C>T (p.Pro253Leu) | POMGNT2 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 570608 | NM_032806.6(POMGNT2):c.1232del (p.Gln411fs) | POMGNT2 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 660661 | NM_032806.6(POMGNT2):c.1042C>T (p.Gln348Ter) | POMGNT2 | Pathogenic | criteria provided, single submitter |
| 694624 | NM_032806.6(POMGNT2):c.590G>A (p.Trp197Ter) | POMGNT2 | Pathogenic | no assertion criteria provided |
| 817989 | NM_032806.6(POMGNT2):c.1258del (p.Ala420fs) | POMGNT2 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 859488 | NM_032806.6(POMGNT2):c.1000_1003del (p.Leu334fs) | POMGNT2 | Pathogenic | criteria provided, single submitter |
| 1058894 | NM_032806.6(POMGNT2):c.1555G>T (p.Glu519Ter) | POMGNT2 | Likely pathogenic | criteria provided, single submitter |
| 3008348 | NM_032806.6(POMGNT2):c.1170T>G (p.Tyr390Ter) | POMGNT2 | Likely pathogenic | criteria provided, single submitter |
| 3780481 | NM_032806.6(POMGNT2):c.1264C>T (p.Gln422Ter) | POMGNT2 | Likely pathogenic | criteria provided, single submitter |
| 262107 | NM_032806.6(POMGNT2):c.561C>T (p.His187=) | POMGNT2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 37208 | NM_032806.6(POMGNT2):c.473G>A (p.Arg158His) | POMGNT2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 382924 | NM_032806.6(POMGNT2):c.450A>G (p.Pro150=) | POMGNT2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 6 · Orphanet: 6 · 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 |
|---|---|---|---|---|
| POMGNT2 | Definitive | Autosomal recessive | muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8 | 6 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| POMGNT2 | Orphanet:899 | Walker-Warburg syndrome |
| ABHD5 | Orphanet:98907 | Neutral lipid storage disease with ichthyosis |
| CRPPA | Orphanet:352479 | ISPD-related limb-girdle muscular dystrophy R20 |
| CRPPA | Orphanet:370980 | Congenital muscular dystrophy without intellectual disability |
| CRPPA | Orphanet:588 | Muscle-eye-brain disease |
| CRPPA | Orphanet:899 | Walker-Warburg syndrome |
Cohort genes → proteins
3 cohort genes, 3 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 3 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| POMGNT2 | HGNC:25902 | ENSG00000144647 | Q8NAT1 | Protein O-linked-mannose beta-1,4-N-acetylglucosaminyltransferase 2 | gencc,clinvar |
| ABHD5 | HGNC:21396 | ENSG00000011198 | Q8WTS1 | 1-acylglycerol-3-phosphate O-acyltransferase ABHD5 | clinvar |
| CRPPA | HGNC:37276 | ENSG00000214960 | A4D126 | D-ribitol-5-phosphate cytidylyltransferase | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| POMGNT2 | Protein O-linked-mannose beta-1,4-N-acetylglucosaminyltransferase 2 | O-linked mannose beta-1,4-N-acetylglucosaminyltransferase that transfers UDP-N-acetyl-D-glucosamine to the 4-position of the mannose to generate N-acetyl-D-glucosamine-beta-1,4-O-D-mannosylprotein. |
| ABHD5 | 1-acylglycerol-3-phosphate O-acyltransferase ABHD5 | Coenzyme A-dependent lysophosphatidic acid acyltransferase that catalyzes the transfer of an acyl group on a lysophosphatidic acid. |
| CRPPA | D-ribitol-5-phosphate cytidylyltransferase | Cytidylyltransferase required for protein O-linked mannosylation. |
Protein-family classification
Druggable: 2 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.67
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 | 9.7× | 0.298 |
| Enzyme (other) | 1 | 4.0× | 0.345 |
| Other/Unknown | 1 | 0.6× | 0.914 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| POMGNT2 | Antibody/Immunoglobulin | yes | 2.4.1.312 | FN3_dom, Glycosyltransferase_61, Ig-like_fold |
| ABHD5 | Other/Unknown | no | AB_hydrolase_1, AB_hydrolase_fold | |
| CRPPA | Enzyme (other) | yes | 2.7.7.40 | ISPD_synthase_CS, Nucleotide-diphossugar_trans, IspD/TarI |
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) | 3 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| cardiac muscle of right atrium | 1 |
| lateral nuclear group of thalamus | 1 |
| right hemisphere of cerebellum | 1 |
| amniotic fluid | 1 |
| lower esophagus mucosa | 1 |
| upper leg skin | 1 |
| calcaneal tendon | 1 |
| corpus callosum | 1 |
| male germ line stem cell (sensu Vertebrata) in testis | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| POMGNT2 | 245 | ubiquitous | marker | lateral nuclear group of thalamus, right hemisphere of cerebellum, cardiac muscle of right atrium |
| ABHD5 | 276 | ubiquitous | marker | amniotic fluid, lower esophagus mucosa, upper leg skin |
| CRPPA | 134 | ubiquitous | yes | corpus callosum, male germ line stem cell (sensu Vertebrata) in testis, calcaneal tendon |
Protein interactions among cohort
Intra-cohort edges: 1.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| ABHD5 | 2,084 |
| CRPPA | 1,629 |
| POMGNT2 | 968 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| CRPPA | POMGNT2 | string_interaction |
Structural data
PDB: 2 · AlphaFold-only: 1 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| POMGNT2 | Q8NAT1 | 3 |
| CRPPA | A4D126 | 1 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| ABHD5 | Q8WTS1 | 87.62 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 6. Enrichment computed across 3 evidence-associated genes (3 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 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| DAG1 core M3 glycosylations | 1 | 634.4× | 0.009 | POMGNT2 |
| Matriglycan biosynthesis on DAG1 | 1 | 271.9× | 0.009 | CRPPA |
| Triglyceride metabolism | 1 | 223.9× | 0.009 | ABHD5 |
| Triglyceride catabolism | 1 | 158.6× | 0.009 | ABHD5 |
| Metabolism of lipids | 1 | 10.5× | 0.111 | ABHD5 |
| Metabolism | 1 | 3.9× | 0.237 | ABHD5 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| protein O-linked glycosylation via mannose | 2 | 624.1× | 4e-05 | POMGNT2, CRPPA |
| negative regulation of triglyceride storage | 1 | 1872.4× | 0.003 | ABHD5 |
| positive regulation of triglyceride catabolic process | 1 | 702.2× | 0.005 | ABHD5 |
| isoprenoid biosynthetic process | 1 | 561.7× | 0.005 | CRPPA |
| phosphatidic acid biosynthetic process | 1 | 170.2× | 0.013 | ABHD5 |
| lipid homeostasis | 1 | 112.3× | 0.016 | ABHD5 |
| protein O-linked glycosylation | 1 | 74.9× | 0.021 | POMGNT2 |
| fatty acid metabolic process | 1 | 64.6× | 0.021 | ABHD5 |
| neuron migration | 1 | 44.6× | 0.027 | POMGNT2 |
| axon guidance | 1 | 30.2× | 0.036 | CRPPA |
| cell differentiation | 1 | 9.7× | 0.100 | ABHD5 |
Therapeutics
Drug target analysis
Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 2
Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Genes with an approved drug
The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.
| Symbol | Example approved molecule |
|---|---|
| ABHD5 | NIFEDIPINE |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| ABHD5 | 8 | 4 |
| POMGNT2 | 0 | 0 |
| CRPPA | 0 | 0 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| NIFEDIPINE | 4 | ABHD5 |
| BENZBROMARONE | 4 | ABHD5 |
| ETHACRYNIC ACID | 4 | ABHD5 |
| MENADIONE | 4 | ABHD5 |
| DISULFIRAM | 4 | ABHD5 |
| INAMRINONE | 4 | ABHD5 |
| CURCUMIN | 3 | ABHD5 |
| EBSELEN | 3 | ABHD5 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 2.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| ABHD5 | 2 | Binding:2 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| POMGNT2 | 2.4.1.312 | protein O-mannose beta-1,4-N-acetylglucosaminyltransferase |
| CRPPA | 2.7.7.40 | D-ribitol-5-phosphate cytidylyltransferase |
Pharmacogenomics
Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.
No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).
Chemical tractability of cohort targets
8 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.
| Compound | Max phase | Cohort target (bioactivity) |
|---|---|---|
| NIFEDIPINE | 4 | ABHD5 |
| BENZBROMARONE | 4 | ABHD5 |
| ETHACRYNIC ACID | 4 | ABHD5 |
| MENADIONE | 4 | ABHD5 |
| DISULFIRAM | 4 | ABHD5 |
| INAMRINONE | 4 | ABHD5 |
| CURCUMIN | 3 | ABHD5 |
| EBSELEN | 3 | ABHD5 |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 1 | ABHD5 |
| B | Phased (≥1) drug, not yet approved | 0 | |
| C | Druggable family + PDB, no drug | 2 | POMGNT2, CRPPA |
| 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) |
|---|---|---|
| POMGNT2 | 0 | — |
| CRPPA | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.