Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12
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Also known as MDDGA12muscular dystrophy-dystroglycanopathy, type A caused by mutation in POMKPOMK muscular dystrophy-dystroglycanopathy, type A
Summary
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12 (MONDO:0014101) is a disease caused by POMK (GenCC Definitive), with 4 cohort genes.
At a glance
- Causal gene: POMK (GenCC Definitive)
- Cohort genes: 4
- ClinVar variants: 247
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, 12 |
| Mondo ID | MONDO:0014101 |
| OMIM | 615249 |
| DOID | DOID:0111235 |
| UMLS | C3808964 |
| MedGen | 815294 |
| GARD | 0015927 |
| Is cancer (heuristic) | no |
Also known as: MDDGA12 · muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12 · muscular dystrophy-dystroglycanopathy, type A caused by mutation in POMK · POMK muscular dystrophy-dystroglycanopathy, type A
Data availability: 247 ClinVar variants · 5 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, 12
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 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
247 retrieved; paginated sample, class counts are floors:
118 uncertain significance, 80 likely benign, 21 pathogenic, 14 conflicting classifications of pathogenicity, 6 benign/likely benign, 5 pathogenic/likely pathogenic, 3 benign
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 4073416 | NM_000723.5(CACNB1):c.124_133del (p.Asp42fs) | CACNB1 | Pathogenic | criteria provided, single submitter |
| 1071646 | NM_032237.5(POMK):c.152del (p.Asp51fs) | POMK | Pathogenic | criteria provided, single submitter |
| 1076046 | NM_032237.5(POMK):c.43C>T (p.Arg15Ter) | POMK | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1323591 | NM_032237.5(POMK):c.907C>T (p.Arg303Ter) | POMK | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 133346 | NM_032237.5(POMK):c.325C>T (p.Gln109Ter) | POMK | Pathogenic | criteria provided, single submitter |
| 1339764 | NM_032237.5(POMK):c.386_387del (p.Leu129fs) | POMK | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1451698 | NM_032237.5(POMK):c.452_455dup (p.His152fs) | POMK | Pathogenic | criteria provided, single submitter |
| 160348 | NM_032237.5(POMK):c.288del (p.Leu97fs) | POMK | Pathogenic | no assertion criteria provided |
| 1911792 | NM_032237.5(POMK):c.754dup (p.Asp252fs) | POMK | Pathogenic | criteria provided, single submitter |
| 2002655 | NM_032237.5(POMK):c.280A>T (p.Arg94Ter) | POMK | Pathogenic | criteria provided, single submitter |
| 2158045 | NM_032237.5(POMK):c.94_98del (p.Thr32fs) | POMK | Pathogenic | criteria provided, single submitter |
| 2165161 | NM_032237.5(POMK):c.247C>T (p.Gln83Ter) | POMK | Pathogenic | criteria provided, single submitter |
| 2634888 | NM_032237.5(POMK):c.398_399del (p.His133fs) | POMK | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 2926947 | NM_032237.5(POMK):c.459del (p.Pro153_Leu154insTer) | POMK | Pathogenic | criteria provided, single submitter |
| 2932937 | NM_032237.5(POMK):c.724dup (p.Val242fs) | POMK | Pathogenic | criteria provided, single submitter |
| 2945834 | NM_032237.5(POMK):c.847del (p.Trp283fs) | POMK | Pathogenic | criteria provided, single submitter |
| 2951325 | NM_032237.5(POMK):c.645T>G (p.Tyr215Ter) | POMK | Pathogenic | criteria provided, single submitter |
| 3752434 | NM_032237.5(POMK):c.61del (p.Val21fs) | POMK | Pathogenic | criteria provided, single submitter |
| 3760619 | NM_032237.5(POMK):c.91_98dup (p.Leu34fs) | POMK | Pathogenic | criteria provided, single submitter |
| 4791932 | NM_032237.5(POMK):c.43del (p.Arg15fs) | POMK | Pathogenic | criteria provided, single submitter |
| 50610 | NM_032237.5(POMK):c.410T>G (p.Leu137Arg) | POMK | Pathogenic | no assertion criteria provided |
| 582702 | NM_032237.5(POMK):c.238_239del (p.Glu80fs) | POMK | Pathogenic | criteria provided, single submitter |
| 651249 | NC_000008.11:g.(?43103539)(43103840_?)del | POMK | Pathogenic | criteria provided, single submitter |
| 817678 | NM_032237.5(POMK):c.43dup (p.Arg15fs) | POMK | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 849427 | NM_032237.5(POMK):c.10C>T (p.Gln4Ter) | POMK | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 949777 | NM_032237.5(POMK):c.282+1G>C | POMK | Pathogenic | criteria provided, single submitter |
| 1312144 | NM_032237.5(POMK):c.256C>T (p.Arg86Cys) | POMK | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 160349 | NM_032237.5(POMK):c.905T>A (p.Val302Asp) | POMK | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 2683017 | NM_032237.5(POMK):c.803del (p.Phe268fs) | POMK | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 432418 | NM_032237.5(POMK):c.20A>G (p.Asn7Ser) | POMK | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 9 · Orphanet: 5 · 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 |
|---|---|---|---|---|
| POMK | Definitive | Autosomal recessive | muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12 | 9 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| POMK | Orphanet:370959 | Congenital muscular dystrophy with cerebellar involvement |
| POMK | Orphanet:445110 | Limb-girdle muscular dystrophy due to POMK deficiency |
| POMK | Orphanet:899 | Walker-Warburg syndrome |
| HGSNAT | Orphanet:791 | Retinitis pigmentosa |
| HGSNAT | Orphanet:79271 | Sanfilippo syndrome type C |
Cohort genes → proteins
4 cohort genes, 4 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 4 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| POMK | HGNC:26267 | ENSG00000185900 | Q9H5K3 | Protein O-mannose kinase | gencc,clinvar |
| CACNB1 | HGNC:1401 | ENSG00000067191 | Q02641 | Voltage-dependent L-type calcium channel subunit beta-1 | clinvar |
| HGSNAT | HGNC:26527 | ENSG00000165102 | Q68CP4 | Heparan-alpha-glucosaminide N-acetyltransferase | clinvar |
| FNTA | HGNC:3782 | ENSG00000168522 | P49354 | Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| POMK | Protein O-mannose kinase | Protein O-mannose kinase that specifically mediates phosphorylation at the 6-position of an O-mannose of the trisaccharide (N-acetylgalactosamine (GalNAc)-beta-1,3-N-acetylglucosamine (GlcNAc)-beta-1,4-mannose) to generate phosphorylated O… |
| CACNB1 | Voltage-dependent L-type calcium channel subunit beta-1 | Regulatory subunit of L-type calcium channels. |
| HGSNAT | Heparan-alpha-glucosaminide N-acetyltransferase | Lysosomal acetyltransferase that acetylates the non-reducing terminal alpha-glucosamine residue of intralysosomal heparin or heparan sulfate, converting it into a substrate for luminal alpha-N-acetyl glucosaminidase. |
| FNTA | Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha | Essential subunit of both the farnesyltransferase and the geranylgeranyltransferase complex. |
Protein-family classification
Druggable: 3 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.75
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) | 2 | 6.0× | 0.112 |
| Kinase | 1 | 6.9× | 0.205 |
| Scaffold/PPI | 1 | 4.3× | 0.212 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| POMK | Kinase | yes | 2.7.1.183 | Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Kinase-like_dom_sf |
| CACNB1 | Scaffold/PPI | no | VDCC_L_bsu, SH3_domain, VDCC_L_b1su | |
| HGSNAT | Enzyme (other) | yes | 2.3.1.78 | HGSNAT_cat |
| FNTA | Enzyme (other) | yes | 2.5.1.58 | Prenyl_trans_a |
Expression context
Cohort genes with no expression data: 0.
3 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 |
|---|---|
| Brodmann (1909) area 10 | 1 |
| middle temporal gyrus | 1 |
| paraflocculus | 1 |
| gastrocnemius | 1 |
| hindlimb stylopod muscle | 1 |
| triceps brachii | 1 |
| cervix squamous epithelium | 1 |
| mucosa of stomach | 1 |
| right uterine tube | 1 |
| esophagus squamous epithelium | 1 |
| gingival epithelium | 1 |
| olfactory bulb | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| POMK | 289 | ubiquitous | yes | paraflocculus, middle temporal gyrus, Brodmann (1909) area 10 |
| CACNB1 | 224 | ubiquitous | marker | gastrocnemius, hindlimb stylopod muscle, triceps brachii |
| HGSNAT | 287 | ubiquitous | marker | mucosa of stomach, right uterine tube, cervix squamous epithelium |
| FNTA | 298 | ubiquitous | marker | esophagus squamous epithelium, gingival epithelium, olfactory bulb |
Protein interactions among cohort
Intra-cohort edges: 3.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| POMK | 1,251 |
| CACNB1 | 1,128 |
| FNTA | 1,080 |
| HGSNAT | 863 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| FNTA | HGSNAT | string_interaction |
| FNTA | POMK | string_interaction |
| HGSNAT | POMK | string_interaction |
Structural data
PDB: 3 · AlphaFold-only: 1 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| FNTA | P49354 | 14 |
| HGSNAT | Q68CP4 | 12 |
| CACNB1 | Q02641 | 6 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| POMK | Q9H5K3 | 91.62 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 27. Enrichment computed across 4 evidence-associated genes (4 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 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| MPS IIIC - Sanfilippo syndrome C | 1 | 2855.0× | 0.009 | HGSNAT |
| DAG1 core M3 glycosylations | 1 | 475.8× | 0.025 | POMK |
| GBP-mediated host defense | 1 | 259.6× | 0.025 | FNTA |
| Presynaptic depolarization and calcium channel opening | 1 | 237.9× | 0.025 | CACNB1 |
| Phase 2 - plateau phase | 1 | 190.3× | 0.025 | CACNB1 |
| Mechanical load activates signaling by PIEZO1 and integrins in osteocytes | 1 | 167.9× | 0.025 | CACNB1 |
| HS-GAG degradation | 1 | 124.1× | 0.025 | HGSNAT |
| Apoptotic cleavage of cellular proteins | 1 | 119.0× | 0.025 | FNTA |
| RAS processing | 1 | 119.0× | 0.025 | FNTA |
| Phase 0 - rapid depolarisation | 1 | 86.5× | 0.031 | CACNB1 |
| Inactivation, recovery and regulation of the phototransduction cascade | 1 | 79.3× | 0.031 | FNTA |
| NCAM signaling for neurite out-growth | 1 | 68.0× | 0.031 | CACNB1 |
| Cellular responses to mechanical stimuli | 1 | 64.9× | 0.031 | CACNB1 |
| NCAM1 interactions | 1 | 62.1× | 0.031 | CACNB1 |
| O-linked glycosylation | 1 | 36.1× | 0.049 | POMK |
| Potential therapeutics for SARS | 1 | 28.6× | 0.058 | FNTA |
| Cardiac conduction | 1 | 27.2× | 0.058 | CACNB1 |
| Muscle contraction | 1 | 19.3× | 0.073 | CACNB1 |
| Transmission across Chemical Synapses | 1 | 19.0× | 0.073 | CACNB1 |
| Axon guidance | 1 | 11.3× | 0.110 | CACNB1 |
| Neuronal System | 1 | 11.1× | 0.110 | CACNB1 |
| Nervous system development | 1 | 10.7× | 0.110 | CACNB1 |
| Cellular responses to stimuli | 1 | 7.9× | 0.142 | CACNB1 |
| Neutrophil degranulation | 1 | 5.8× | 0.183 | HGSNAT |
| Post-translational protein modification | 1 | 4.8× | 0.208 | POMK |
| Developmental Biology | 1 | 3.6× | 0.259 | CACNB1 |
| Metabolism of proteins | 1 | 3.1× | 0.286 | POMK |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 4 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| peptide pheromone maturation | 1 | 4213.0× | 0.006 | FNTA |
| protein farnesylation | 1 | 1404.3× | 0.006 | FNTA |
| protein geranylgeranylation | 1 | 702.2× | 0.006 | FNTA |
| regulation of microtubule-based movement | 1 | 702.2× | 0.006 | FNTA |
| positive regulation of muscle contraction | 1 | 601.9× | 0.006 | CACNB1 |
| carbohydrate phosphorylation | 1 | 526.6× | 0.006 | POMK |
| heparan sulfate proteoglycan catabolic process | 1 | 468.1× | 0.006 | HGSNAT |
| skeletal muscle acetylcholine-gated channel clustering | 1 | 468.1× | 0.006 | FNTA |
| positive regulation of skeletal muscle acetylcholine-gated channel clustering | 1 | 468.1× | 0.006 | FNTA |
| regulation of calcium ion transmembrane transport via high voltage-gated calcium channel | 1 | 421.3× | 0.006 | CACNB1 |
| lysosomal transport | 1 | 175.5× | 0.011 | HGSNAT |
| protein complex oligomerization | 1 | 168.5× | 0.011 | HGSNAT |
| positive regulation of Rac protein signal transduction | 1 | 162.0× | 0.011 | FNTA |
| Rac protein signal transduction | 1 | 140.4× | 0.012 | FNTA |
| neuromuscular process | 1 | 131.7× | 0.012 | POMK |
| cellular response to amyloid-beta | 1 | 98.0× | 0.015 | CACNB1 |
| sensory perception of pain | 1 | 93.6× | 0.015 | POMK |
| learning or memory | 1 | 60.2× | 0.022 | POMK |
| protein O-linked glycosylation | 1 | 56.2× | 0.022 | POMK |
| calcium ion transmembrane transport | 1 | 52.7× | 0.023 | CACNB1 |
| calcium ion transport | 1 | 45.3× | 0.025 | CACNB1 |
| transforming growth factor beta receptor signaling pathway | 1 | 39.8× | 0.027 | FNTA |
| brain development | 1 | 19.9× | 0.051 | POMK |
| chemical synaptic transmission | 1 | 19.3× | 0.051 | CACNB1 |
Therapeutics
Drug target analysis
Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 2
Druggability breadth: 2 of 4 evidence-associated genes (50%) 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 |
|---|---|
| CACNB1 | NIMODIPINE |
| FNTA | CORTISONE ACETATE |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| FNTA | 6 | 4 |
| CACNB1 | 3 | 4 |
| POMK | 0 | 0 |
| HGSNAT | 0 | 0 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| NIMODIPINE | 4 | CACNB1 |
| TACRINE | 4 | CACNB1 |
| CORTISONE ACETATE | 4 | FNTA |
| LONAFARNIB | 4 | FNTA |
| TIPIFARNIB | 3 | FNTA |
| Z160 | 2 | CACNB1 |
| L-778123 FREE BASE | 1 | FNTA |
| GGTI-2418 | 1 | FNTA |
| BMS-214662 | 1 | FNTA |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 3.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| FNTA | 513 | Binding:438, Functional:75 |
| CACNB1 | 19 | Binding:19 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| POMK | 2.7.1.183 | glycoprotein-mannosyl O6-kinase |
| HGSNAT | 2.3.1.78 | heparan-alpha-glucosaminide N-acetyltransferase |
| FNTA | 2.5.1.58, 2.5.1.59 | protein farnesyltransferase, protein geranylgeranyltransferase type I |
Cohort genes with high screening signal
≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.
| Symbol | ChEMBL assays |
|---|---|
| FNTA | 513 |
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
9 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) |
|---|---|---|
| NIMODIPINE | 4 | CACNB1 |
| TACRINE | 4 | CACNB1 |
| CORTISONE ACETATE | 4 | FNTA |
| LONAFARNIB | 4 | FNTA |
| TIPIFARNIB | 3 | FNTA |
| Z160 | 2 | CACNB1 |
| L-778123 FREE BASE | 1 | FNTA |
| GGTI-2418 | 1 | FNTA |
| BMS-214662 | 1 | FNTA |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 2 | CACNB1, FNTA |
| B | Phased (≥1) drug, not yet approved | 0 | |
| C | Druggable family + PDB, no drug | 1 | HGSNAT |
| D | Druggable family + AlphaFold only, no drug | 1 | POMK |
| 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) |
|---|---|---|
| POMK | 0 | — |
| HGSNAT | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.