muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7
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Also known as ISPD muscular dystrophy-dystroglycanopathy, type AMDDGA7muscular dystrophy-dystroglycanopathy, type A caused by mutation in ISPDWalker-Warburg syndrome or muscle-eye-brain disease, ISPD-related
Summary
muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7 (MONDO:0013835) is a disease caused by CRPPA (GenCC Definitive), with 3 cohort genes.
At a glance
- Causal gene: CRPPA (GenCC Definitive)
- Cohort genes: 3
- ClinVar variants: 456
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, 7 |
| Mondo ID | MONDO:0013835 |
| OMIM | 614643 |
| DOID | DOID:0111234 |
| UMLS | C3553330 |
| MedGen | 766244 |
| GARD | 0015829 |
| Is cancer (heuristic) | no |
Also known as: ISPD muscular dystrophy-dystroglycanopathy, type A · MDDGA7 · muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7 · muscular dystrophy-dystroglycanopathy, type A caused by mutation in ISPD · Walker-Warburg syndrome or muscle-eye-brain disease, ISPD-related
Data availability: 456 ClinVar variants · 3 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, 7
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, 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
456 retrieved; paginated sample, class counts are floors:
173 uncertain significance, 136 likely benign, 58 pathogenic, 51 conflicting classifications of pathogenicity, 12 likely pathogenic, 11 benign, 9 benign/likely benign, 6 pathogenic/likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1072533 | NC_000007.13:g.(?16445666)(16445982_?)del | CRPPA | Pathogenic | criteria provided, single submitter |
| 1072534 | NC_000007.13:g.(?16131310)(16255832_?)del | CRPPA | Pathogenic | criteria provided, single submitter |
| 1076250 | NM_001101426.4(CRPPA):c.550C>T (p.Arg184Ter) | CRPPA | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1252045 | NM_001101426.4(CRPPA):c.790-1G>C | CRPPA | Pathogenic | criteria provided, single submitter |
| 156455 | NM_001101426.4(CRPPA):c.1105GTT[3] (p.Val372del) | CRPPA | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1680626 | NC_000007.13:g.(?16341026)(16341111_?)del | CRPPA | Pathogenic | criteria provided, single submitter |
| 1680627 | NC_000007.13:g.(?16341026)(16415886_?)del | CRPPA | Pathogenic | criteria provided, single submitter |
| 1680628 | NC_000007.13:g.(?16348128)(16445982_?)del | CRPPA | Pathogenic | criteria provided, single submitter |
| 1680630 | NC_000007.13:g.(?16460671)(16460947_?)del | CRPPA | Pathogenic | criteria provided, single submitter |
| 1805380 | NM_001101426.4(CRPPA):c.258-2A>G | CRPPA | Pathogenic | criteria provided, single submitter |
| 1983342 | NM_001101426.4(CRPPA):c.79_80del (p.Thr27fs) | CRPPA | Pathogenic | criteria provided, single submitter |
| 2070304 | NM_001101426.4(CRPPA):c.17_24dup (p.Ala9fs) | CRPPA | Pathogenic | criteria provided, single submitter |
| 2078955 | NM_001101426.4(CRPPA):c.534+1del | CRPPA | Pathogenic | criteria provided, single submitter |
| 2122850 | NM_001101426.4(CRPPA):c.1092C>A (p.Cys364Ter) | CRPPA | Pathogenic | criteria provided, single submitter |
| 2142758 | NM_001101426.4(CRPPA):c.1137dup (p.Lys380Ter) | CRPPA | Pathogenic | criteria provided, single submitter |
| 2423709 | NC_000007.13:g.(?16415697)(16460947_?)del | CRPPA | Pathogenic | criteria provided, single submitter |
| 2423710 | NC_000007.13:g.(?16297995)(16317871_?)del | CRPPA | Pathogenic | criteria provided, single submitter |
| 2423714 | NC_000007.13:g.(?16131320)(16460947_?)del | CRPPA | Pathogenic | criteria provided, single submitter |
| 2423715 | NC_000007.13:g.(?16131320)(16255842_?)del | CRPPA | Pathogenic | criteria provided, single submitter |
| 279985 | NM_001101426.4(CRPPA):c.53dup (p.Ser19Glufs) | CRPPA | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 282846 | NM_001101426.4(CRPPA):c.643C>T (p.Gln215Ter) | CRPPA | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 287941 | NM_001101426.4(CRPPA):c.258-1G>C | CRPPA | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 2924564 | NM_001101426.4(CRPPA):c.896del (p.Gly299fs) | CRPPA | Pathogenic | criteria provided, single submitter |
| 2930168 | NM_001101426.4(CRPPA):c.337C>T (p.Gln113Ter) | CRPPA | Pathogenic | criteria provided, single submitter |
| 2941204 | NM_001101426.4(CRPPA):c.6_13dup (p.Pro5fs) | CRPPA | Pathogenic | criteria provided, single submitter |
| 31561 | NM_001101426.4(CRPPA):c.1120-1G>T | CRPPA | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 31562 | NM_001101426.3(CRPPA):c.(535_684)+6399_(535_684)+14526del | CRPPA | Pathogenic | no assertion criteria provided |
| 31563 | NM_001101426.4(CRPPA):c.789+2T>G | CRPPA | Pathogenic | no assertion criteria provided |
| 31565 | NM_001101426.4(CRPPA):c.647C>A (p.Ala216Asp) | CRPPA | Pathogenic | no assertion criteria provided |
| 31566 | NM_001101426.4(CRPPA):c.832A>T (p.Lys278Ter) | CRPPA | Pathogenic | no assertion criteria provided |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 7 · Orphanet: 4 · 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 |
|---|---|---|---|---|
| CRPPA | Definitive | Autosomal recessive | muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7 | 7 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| 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, 2 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 3 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| CRPPA | HGNC:37276 | ENSG00000214960 | A4D126 | D-ribitol-5-phosphate cytidylyltransferase | gencc,clinvar |
| LRRC72 | HGNC:42972 | ENSG00000205858 | A6NJI9 | Leucine-rich repeat-containing protein 72 | clinvar |
| CRPPA-AS1 | HGNC:48962 | ENSG00000229688 | CRPPA antisense RNA 1 | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| CRPPA | D-ribitol-5-phosphate cytidylyltransferase | Cytidylyltransferase required for protein O-linked mannosylation. |
Protein-family classification
Druggable: 1 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.33
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) | 1 | 4.0× | 0.460 |
| Other/Unknown | 2 | 1.2× | 0.587 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| CRPPA | Enzyme (other) | yes | 2.7.7.40 | ISPD_synthase_CS, Nucleotide-diphossugar_trans, IspD/TarI |
| LRRC72 | Other/Unknown | no | Leu-rich_rpt, LRR_dom_sf, LRC72 | |
| CRPPA-AS1 | 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) | 3 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| male germ line stem cell (sensu Vertebrata) in testis | 3 |
| left testis | 2 |
| calcaneal tendon | 1 |
| corpus callosum | 1 |
| right testis | 1 |
| sperm | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| CRPPA | 134 | ubiquitous | yes | corpus callosum, male germ line stem cell (sensu Vertebrata) in testis, calcaneal tendon |
| LRRC72 | 21 | tissue_specific | marker | male germ line stem cell (sensu Vertebrata) in testis, left testis, right testis |
| CRPPA-AS1 | 147 | tissue_specific | marker | sperm, male germ line stem cell (sensu Vertebrata) in testis, left testis |
Protein interactions among cohort
Intra-cohort edges: 1.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| CRPPA | 1,629 |
| LRRC72 | 370 |
| CRPPA-AS1 | 0 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| CRPPA | LRRC72 | string_interaction |
Structural data
PDB: 1 · AlphaFold-only: 1 · No structure: 1
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| CRPPA | A4D126 | 1 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| LRRC72 | A6NJI9 | 79.40 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 3 evidence-associated genes (1 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 1 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 | 1 | 815.7× | 0.001 | CRPPA |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| isoprenoid biosynthetic process | 1 | 1685.2× | 0.002 | CRPPA |
| protein O-linked glycosylation via mannose | 1 | 936.2× | 0.002 | CRPPA |
| axon guidance | 1 | 90.6× | 0.011 | CRPPA |
Therapeutics
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 3
Druggability breadth: 0 of 3 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 |
|---|---|---|
| CRPPA | 0 | 0 |
| LRRC72 | 0 | 0 |
| CRPPA-AS1 | 0 | 0 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 1.
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| CRPPA | 2.7.7.40 | D-ribitol-5-phosphate cytidylyltransferase |
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 | 1 | CRPPA |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 2 | LRRC72, CRPPA-AS1 |
Undrugged target profiles
3 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| CRPPA | 0 | — |
| LRRC72 | 0 | — |
| CRPPA-AS1 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.