muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1
diseaseOn this page
Also known as MDDGA1muscle-eye-brain-POMT1 relatedmuscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies) type A, 1muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1
Summary
muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1 (MONDO:0009364) is a disease caused by POMT1 (GenCC Definitive), with 7 cohort genes. The dominant Reactome pathway is Matriglycan biosynthesis on DAG1 (5 cohort genes).
At a glance
- Causal gene: POMT1 (GenCC Definitive)
- Cohort genes: 7
- ClinVar variants: 306
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 A1 |
| Mondo ID | MONDO:0009364 |
| OMIM | 236670 |
| DOID | DOID:0111237 |
| NCIT | C128118 |
| UMLS | C4284790 |
| MedGen | 924974 |
| GARD | 0024665 |
| Is cancer (heuristic) | no |
Also known as: MDDGA1 · muscle-eye-brain-POMT1 related · muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies) type A, 1 · muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1
Data availability: 306 ClinVar variants · 4 GenCC gene-disease records · 1 cell line.
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 A1
Related subtypes (13): 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, 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
306 retrieved; paginated sample, class counts are floors:
101 uncertain significance, 55 pathogenic/likely pathogenic, 48 conflicting classifications of pathogenicity, 41 likely pathogenic, 31 pathogenic, 12 benign, 11 benign/likely benign, 7 likely benign
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 183334 | NM_006876.3(B4GAT1):c.821_822insTT (p.Glu274fs) | B4GAT1 | Pathogenic/Likely pathogenic | no assertion criteria provided |
| 197347 | NM_024301.5(FKRP):c.947C>G (p.Pro316Arg) | FKRP | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 4220 | NM_024301.5(FKRP):c.1343C>T (p.Pro448Leu) | FKRP | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 4221 | NM_024301.5(FKRP):c.826C>A (p.Leu276Ile) | FKRP | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 4232 | NM_024301.5(FKRP):c.899T>C (p.Val300Ala) | FKRP | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 4235 | NM_024301.5(FKRP):c.1387A>G (p.Asn463Asp) | FKRP | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 550361 | NM_024301.5(FKRP):c.928G>T (p.Glu310Ter) | FKRP | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 551007 | NM_024301.5(FKRP):c.266C>T (p.Pro89Leu) | FKRP | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 554104 | NM_024301.5(FKRP):c.778G>T (p.Glu260Ter) | FKRP | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 654883 | NM_024301.5(FKRP):c.1296G>A (p.Trp432Ter) | FKRP | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 664273 | NM_024301.5(FKRP):c.948del (p.Cys317fs) | FKRP | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 167069 | NM_001079802.2(FKTN):c.411C>A (p.Cys137Ter) | FKTN | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 225359 | NM_001079802.2(FKTN):c.607C>T (p.Arg203Ter) | FKTN | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 281839 | NM_001079802.2(FKTN):c.330dup (p.Thr111fs) | FKTN | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 283622 | NM_001079802.2(FKTN):c.456_457del (p.Ser154fs) | FKTN | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 3203 | NM_001079802.2(FKTN):c.1167dup (p.Phe390fs) | FKTN | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 3204 | NM_001079802.2(FKTN):c.527T>C (p.Phe176Ser) | FKTN | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 496331 | NM_001079802.2(FKTN):c.648-1243G>T | FKTN | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1066221 | NM_001077365.2(POMT1):c.1176-2A>G | POMT1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1120088 | NM_001077365.2(POMT1):c.1255C>T (p.Gln419Ter) | POMT1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1192212 | NM_001077365.2(POMT1):c.1272+1G>A | POMT1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1252077 | NM_001077365.2(POMT1):c.1175+3del | POMT1 | Pathogenic | no assertion criteria provided |
| 1343631 | NM_001077365.2(POMT1):c.2040_2050del (p.Val681fs) | POMT1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1360015 | NM_001077365.2(POMT1):c.270_280delAATTGGAGCAG (p.Gly92fs) | POMT1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1399708 | NM_001077365.2(POMT1):c.97C>T (p.Arg33Ter) | POMT1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1453137 | NM_001077365.2(POMT1):c.1364del (p.Lys455fs) | POMT1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1458255 | NM_001077365.2(POMT1):c.130G>A (p.Glu44Lys) | POMT1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1497287 | NM_001077365.2(POMT1):c.313C>T (p.Arg105Cys) | POMT1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1686087 | NM_001077365.2(POMT1):c.986+1G>A | POMT1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1696829 | NM_001077365.2(POMT1):c.1417G>C (p.Gly473Arg) | POMT1 | Pathogenic | criteria provided, single submitter |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 12 · Orphanet: 31 · 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 |
|---|---|---|---|---|
| POMT1 | Definitive | Autosomal recessive | muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1 | 12 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| POMT1 | Orphanet:370959 | Congenital muscular dystrophy with cerebellar involvement |
| POMT1 | Orphanet:370968 | Congenital muscular dystrophy with intellectual disability |
| POMT1 | Orphanet:370980 | Congenital muscular dystrophy without intellectual disability |
| POMT1 | Orphanet:588 | Muscle-eye-brain disease |
| POMT1 | Orphanet:86812 | POMT1-related limb-girdle muscular dystrophy R11 |
| POMT1 | Orphanet:899 | Walker-Warburg syndrome |
| B4GAT1 | Orphanet:899 | Walker-Warburg syndrome |
| FKRP | Orphanet:34515 | FKRP-related limb-girdle muscular dystrophy R9 |
| FKRP | Orphanet:370959 | Congenital muscular dystrophy with cerebellar involvement |
| FKRP | Orphanet:370968 | Congenital muscular dystrophy with intellectual disability |
| FKRP | Orphanet:370980 | Congenital muscular dystrophy without intellectual disability |
| FKRP | Orphanet:588 | Muscle-eye-brain disease |
| FKRP | Orphanet:899 | Walker-Warburg syndrome |
| POMT2 | Orphanet:206559 | POMT2-related limb-girdle muscular dystrophy R14 |
| POMT2 | Orphanet:370959 | Congenital muscular dystrophy with cerebellar involvement |
| POMT2 | Orphanet:370968 | Congenital muscular dystrophy with intellectual disability |
| POMT2 | Orphanet:588 | Muscle-eye-brain disease |
| POMT2 | Orphanet:899 | Walker-Warburg syndrome |
| 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 |
| FKTN | Orphanet:154 | Familial isolated dilated cardiomyopathy |
| FKTN | Orphanet:206554 | Fukutin-related limb-girdle muscular dystrophy R13 |
| FKTN | Orphanet:272 | Congenital muscular dystrophy, Fukuyama type |
| FKTN | Orphanet:370980 | Congenital muscular dystrophy without intellectual disability |
| FKTN | Orphanet:588 | Muscle-eye-brain disease |
| FKTN | Orphanet:899 | Walker-Warburg syndrome |
| LARGE1 | Orphanet:370968 | Congenital muscular dystrophy with intellectual disability |
| LARGE1 | Orphanet:588 | Muscle-eye-brain disease |
| LARGE1 | Orphanet:899 | Walker-Warburg syndrome |
Cohort genes → proteins
7 cohort genes, 7 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 7 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| POMT1 | HGNC:9202 | ENSG00000130714 | Q9Y6A1 | Protein O-mannosyl-transferase 1 | gencc,clinvar |
| B4GAT1 | HGNC:15685 | ENSG00000174684 | O43505 | Beta-1,4-glucuronyltransferase 1 | clinvar |
| FKRP | HGNC:17997 | ENSG00000181027 | Q9H9S5 | Ribitol 5-phosphate transferase FKRP | clinvar |
| POMT2 | HGNC:19743 | ENSG00000009830 | Q9UKY4 | Protein O-mannosyl-transferase 2 | clinvar |
| DAG1 | HGNC:2666 | ENSG00000173402 | Q14118 | Dystroglycan 1 | clinvar |
| FKTN | HGNC:3622 | ENSG00000106692 | O75072 | Ribitol-5-phosphate transferase FKTN | clinvar |
| LARGE1 | HGNC:6511 | ENSG00000133424 | O95461 | Xylosyl- and glucuronyltransferase LARGE1 | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| POMT1 | Protein O-mannosyl-transferase 1 | Transfers mannosyl residues to the hydroxyl group of serine or threonine residues. |
| B4GAT1 | Beta-1,4-glucuronyltransferase 1 | Beta-1,4-glucuronyltransferase involved in O-mannosylation of alpha-dystroglycan (DAG1). |
| FKRP | Ribitol 5-phosphate transferase FKRP | Catalyzes the transfer of a ribitol 5-phosphate from CDP-L-ribitol to the ribitol 5-phosphate previously attached by FKTN/fukutin to the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-beta-3-N-acetylglucosamine-beta-4-(phos… |
| POMT2 | Protein O-mannosyl-transferase 2 | Transfers mannosyl residues to the hydroxyl group of serine or threonine residues. |
| 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… |
| FKTN | Ribitol-5-phosphate transferase FKTN | Catalyzes the transfer of a ribitol-phosphate from CDP-ribitol to the distal N-acetylgalactosamine of the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-beta-3-N-acetylglucosamine-beta-4-(phosphate-6-)mannose), a carbohydra… |
| LARGE1 | Xylosyl- and glucuronyltransferase LARGE1 | Bifunctional glycosyltransferase with both alpha-1,3-xylosyltransferase and beta-1,3-glucuronyltransferase activities involved in the maturation of alpha-dystroglycan (DAG1) by glycosylation leading to DAG1 binding to laminin G-like domain… |
Protein-family classification
Druggable: 5 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.71
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) | 4 | 6.8× | 0.004 |
| Antibody/Immunoglobulin | 1 | 4.2× | 0.325 |
| Other/Unknown | 2 | 0.5× | 0.968 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| POMT1 | Enzyme (other) | yes | 2.4.1.109 | ArnT-like_N, MIR_motif, PMT-like |
| B4GAT1 | Enzyme (other) | yes | 2.4.1.149 | B4GAT1 |
| FKRP | Other/Unknown | no | LicD/FKTN/FKRP_NTP_transf, LicD_transferase, FKRP_N | |
| POMT2 | Enzyme (other) | yes | 2.4.1.109 | ArnT-like_N, MIR_motif, PMT-like |
| DAG1 | Antibody/Immunoglobulin | yes | Cadg, DAG1_C, Ig-like_fold | |
| FKTN | Other/Unknown | no | LicD/FKTN/FKRP_NTP_transf, FKTN/MNN-like, FKTN_N | |
| LARGE1 | Enzyme (other) | yes | 2.4.1.B80 | Glyco_trans_8, Nucleotide-diphossugar_trans, Xyl/GlcA_transferase |
Expression context
Cohort genes with no expression data: 0.
5 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) | 7 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| cerebellar cortex | 1 |
| cerebellar hemisphere | 1 |
| right hemisphere of cerebellum | 1 |
| endothelial cell | 1 |
| middle temporal gyrus | 1 |
| pons | 1 |
| cardiac muscle of right atrium | 1 |
| hindlimb stylopod muscle | 1 |
| left ventricle myocardium | 1 |
| left testis | 1 |
| right testis | 1 |
| testis | 1 |
| dorsal root ganglion | 1 |
| olfactory bulb | 1 |
| trigeminal ganglion | 1 |
| adrenal tissue | 1 |
| calcaneal tendon | 1 |
| germinal epithelium of ovary | 1 |
| apex of heart | 1 |
| cardiac ventricle | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| POMT1 | 264 | ubiquitous | marker | right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex |
| B4GAT1 | 285 | ubiquitous | marker | endothelial cell, middle temporal gyrus, pons |
| FKRP | 230 | ubiquitous | marker | left ventricle myocardium, cardiac muscle of right atrium, hindlimb stylopod muscle |
| POMT2 | 222 | ubiquitous | yes | right testis, left testis, testis |
| DAG1 | 299 | ubiquitous | marker | olfactory bulb, trigeminal ganglion, dorsal root ganglion |
| FKTN | 277 | ubiquitous | yes | calcaneal tendon, adrenal tissue, germinal epithelium of ovary |
| LARGE1 | 233 | tissue_specific | marker | heart left ventricle, cardiac ventricle, apex of heart |
Protein interactions among cohort
Intra-cohort edges: 21.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| DAG1 | 2,301 |
| POMT1 | 1,475 |
| FKRP | 1,436 |
| POMT2 | 1,284 |
| FKTN | 1,226 |
| B4GAT1 | 823 |
| LARGE1 | 551 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| B4GAT1 | DAG1 | string_interaction |
| B4GAT1 | FKRP | biogrid_interaction, intact, string_interaction |
| B4GAT1 | FKTN | biogrid_interaction, intact, string_interaction |
| B4GAT1 | LARGE1 | intact |
| B4GAT1 | POMT1 | intact, string_interaction |
| B4GAT1 | POMT2 | string_interaction |
| DAG1 | FKRP | string_interaction |
| DAG1 | FKTN | string_interaction |
| DAG1 | LARGE1 | string_interaction |
| DAG1 | POMT1 | string_interaction |
| DAG1 | POMT2 | string_interaction |
| FKRP | FKTN | intact, string_interaction |
| FKRP | LARGE1 | string_interaction |
| FKRP | POMT1 | string_interaction |
| FKRP | POMT2 | string_interaction |
| FKTN | LARGE1 | string_interaction |
| FKTN | POMT1 | string_interaction |
| FKTN | POMT2 | string_interaction |
| LARGE1 | POMT1 | string_interaction |
| LARGE1 | POMT2 | string_interaction |
| POMT1 | POMT2 | intact, string_interaction |
Structural data
PDB: 3 · AlphaFold-only: 4 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| FKRP | Q9H9S5 | 8 |
| DAG1 | Q14118 | 8 |
| LARGE1 | O95461 | 4 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| FKTN | O75072 | 92.48 |
| B4GAT1 | O43505 | 88.46 |
| POMT1 | Q9Y6A1 | 88.09 |
| POMT2 | Q9UKY4 | 87.96 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 26. Enrichment computed across 7 evidence-associated genes (7 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 7 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Matriglycan biosynthesis on DAG1 | 5 | 582.6× | 7e-13 | B4GAT1, FKRP, DAG1, FKTN, LARGE1 |
| Defective POMT2 causes MDDGA2, MDDGB2 and MDDGC2 | 3 | 1631.4× | 1e-09 | POMT1, POMT2, DAG1 |
| Defective POMT1 causes MDDGA1, MDDGB1 and MDDGC1 | 3 | 1631.4× | 1e-09 | POMT1, POMT2, DAG1 |
| DAG1 core M1 glycosylations | 3 | 1223.6× | 4e-09 | POMT1, POMT2, DAG1 |
| DAG1 core M2 glycosylations | 3 | 978.9× | 7e-09 | POMT1, POMT2, DAG1 |
| DAG1 core M3 glycosylations | 3 | 815.7× | 1e-08 | POMT1, POMT2, DAG1 |
| Defective LARGE causes MDDGA6 and MDDGB6 | 2 | 1087.6× | 4e-06 | B4GAT1, LARGE1 |
| Regulation of CDH1 posttranslational processing and trafficking to plasma membrane | 2 | 96.0× | 6e-04 | POMT1, POMT2 |
| Diseases associated with O-glycosylation of proteins | 2 | 61.6× | 0.001 | B4GAT1, LARGE1 |
| O-linked glycosylation | 2 | 41.3× | 0.003 | B4GAT1, LARGE1 |
| Defective POMGNT1 causes MDDGA3, MDDGB3 and MDDGC3 | 1 | 815.7× | 0.003 | DAG1 |
| Diseases of glycosylation | 2 | 37.5× | 0.003 | B4GAT1, LARGE1 |
| Diseases of metabolism | 2 | 23.0× | 0.006 | B4GAT1, LARGE1 |
| Keratan sulfate/keratin metabolism | 1 | 70.9× | 0.026 | B4GAT1 |
| Keratan sulfate biosynthesis | 1 | 54.4× | 0.031 | B4GAT1 |
| EGR2 and SOX10-mediated initiation of Schwann cell myelination | 1 | 52.6× | 0.031 | DAG1 |
| Formation of the dystrophin-glycoprotein complex (DGC) | 1 | 44.1× | 0.034 | DAG1 |
| Glycosaminoglycan metabolism | 1 | 31.4× | 0.045 | B4GAT1 |
| Non-integrin membrane-ECM interactions | 1 | 22.1× | 0.059 | DAG1 |
| ECM proteoglycans | 1 | 21.5× | 0.059 | DAG1 |
| Post-translational protein modification | 2 | 5.5× | 0.059 | B4GAT1, LARGE1 |
| Metabolism of carbohydrates and carbohydrate derivatives | 1 | 17.2× | 0.067 | B4GAT1 |
| Regulation of expression of SLITs and ROBOs | 1 | 9.9× | 0.105 | DAG1 |
| Disease | 2 | 3.7× | 0.105 | B4GAT1, LARGE1 |
| Metabolism of proteins | 2 | 3.5× | 0.109 | B4GAT1, LARGE1 |
| Metabolism | 1 | 1.7× | 0.468 | B4GAT1 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 7 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 | 6 | 802.5× | 5e-16 | POMT1, B4GAT1, FKRP, POMT2, FKTN, LARGE1 |
| basement membrane organization | 5 | 364.8× | 3e-11 | FKRP, POMT2, DAG1, FKTN, LARGE1 |
| skeletal muscle fiber differentiation | 3 | 722.2× | 2e-07 | FKRP, FKTN, LARGE1 |
| skeletal muscle tissue regeneration | 3 | 380.1× | 1e-06 | FKRP, DAG1, LARGE1 |
| connective tissue development | 2 | 1203.7× | 2e-05 | FKRP, LARGE1 |
| localization of cell | 2 | 802.5× | 5e-05 | FKRP, LARGE1 |
| reactive gliosis | 2 | 687.8× | 5e-05 | POMT2, LARGE1 |
| protein O-linked glycosylation | 3 | 96.3× | 5e-05 | POMT1, FKTN, LARGE1 |
| nerve development | 2 | 267.5× | 3e-04 | DAG1, LARGE1 |
| positive regulation of Rac protein signal transduction | 2 | 185.2× | 6e-04 | DAG1, LARGE1 |
| dentate gyrus development | 2 | 178.3× | 6e-04 | POMT2, LARGE1 |
| heart morphogenesis | 2 | 107.0× | 0.002 | FKRP, DAG1 |
| muscle attachment | 1 | 2407.4× | 0.003 | DAG1 |
| pentitol metabolic process | 1 | 2407.4× | 0.003 | FKRP |
| nerve maturation | 1 | 2407.4× | 0.003 | DAG1 |
| post-embryonic hindlimb morphogenesis | 1 | 2407.4× | 0.003 | LARGE1 |
| filtration diaphragm assembly | 1 | 2407.4× | 0.003 | FKRP |
| calcium-dependent cell-matrix adhesion | 1 | 1203.7× | 0.005 | DAG1 |
| pentose metabolic process | 1 | 1203.7× | 0.005 | FKRP |
| principal sensory nucleus of trigeminal nerve development | 1 | 802.5× | 0.007 | LARGE1 |
| synaptic assembly at neuromuscular junction | 1 | 802.5× | 0.007 | LARGE1 |
| retrograde trans-synaptic signaling by trans-synaptic protein complex | 1 | 802.5× | 0.007 | DAG1 |
| neuron migration | 2 | 38.2× | 0.007 | FKRP, LARGE1 |
| extracellular matrix organization | 2 | 34.9× | 0.007 | POMT1, DAG1 |
| creatine metabolic process | 1 | 601.9× | 0.008 | FKRP |
| negative regulation of muscle cell apoptotic process | 1 | 601.9× | 0.008 | LARGE1 |
| oxygen metabolic process | 1 | 601.9× | 0.008 | FKRP |
| maintenance of protein localization in endoplasmic reticulum | 1 | 481.5× | 0.009 | FKRP |
| walking behavior | 1 | 401.2× | 0.010 | LARGE1 |
| axon guidance | 2 | 25.9× | 0.010 | B4GAT1, DAG1 |
Therapeutics
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 7
Druggability breadth: 2 of 7 evidence-associated genes (29%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| POMT1 | 0 | 0 |
| B4GAT1 | 0 | 0 |
| FKRP | 0 | 0 |
| POMT2 | 0 | 0 |
| DAG1 | 0 | 0 |
| FKTN | 0 | 0 |
| LARGE1 | 0 | 0 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 4.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| DAG1 | 4 | Binding:4 |
| LARGE1 | 2 | Functional:2 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| POMT1 | 2.4.1.109 | dolichyl-phosphate-mannose-protein mannosyltransferase |
| B4GAT1 | 2.4.1.149 | N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase |
| POMT2 | 2.4.1.109 | dolichyl-phosphate-mannose-protein mannosyltransferase |
| LARGE1 | 2.4.1.B80, 2.4.2.B18 | , |
Pharmacogenomics
Cohort genes with a PharmGKB record: 7; 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, LARGE1 |
| D | Druggable family + AlphaFold only, no drug | 3 | POMT1, B4GAT1, POMT2 |
| E | Difficult family or no structure, no drug | 2 | FKRP, FKTN |
Undrugged target profiles
7 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| POMT1 | 0 | — |
| B4GAT1 | 0 | — |
| FKRP | 0 | — |
| POMT2 | 0 | — |
| DAG1 | 4 | — |
| FKTN | 0 | — |
| LARGE1 | 2 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.