muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A5

disease

On this page

Also known as MDDGA5muscle-eye-brain-FKRP relatedmuscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 5

Summary

muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A5 (MONDO:0013157) is a disease caused by FKRP (GenCC Definitive), with 2 cohort genes.

At a glance

Causal gene: FKRP (GenCC Definitive)
Cohort genes: 2
ClinVar variants: 175

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 A5
Mondo ID	MONDO:0013157
OMIM	613153
DOID	DOID:0111241
UMLS	C3150413
MedGen	461763
GARD	0015625
Is cancer (heuristic)	no

Also known as: MDDGA5 · muscle-eye-brain-FKRP related · muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 5

Data availability: 175 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 A5

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

175 retrieved; paginated sample, class counts are floors:

49 uncertain significance, 41 pathogenic/likely pathogenic, 35 likely pathogenic, 29 conflicting classifications of pathogenicity, 10 pathogenic, 5 benign/likely benign, 4 likely benign, 2 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1071118	NM_024301.5(FKRP):c.540_570dup (p.Cys191fs)	FKRP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1073047	NM_024301.5(FKRP):c.511_523del (p.Leu171fs)	FKRP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
120180	NM_024301.5(FKRP):c.1A>G (p.Met1Val)	FKRP	Pathogenic	criteria provided, single submitter
1363110	NM_024301.5(FKRP):c.1335_1336del (p.Leu446fs)	FKRP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1365203	NM_024301.5(FKRP):c.892G>T (p.Gly298Ter)	FKRP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1920325	NM_024301.5(FKRP):c.949del (p.Cys317fs)	FKRP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1929555	NM_024301.5(FKRP):c.692G>A (p.Trp231Ter)	FKRP	Pathogenic	criteria provided, multiple submitters, no conflicts
1934796	NM_024301.5(FKRP):c.712_713del (p.Leu238fs)	FKRP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
197347	NM_024301.5(FKRP):c.947C>G (p.Pro316Arg)	FKRP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2138310	NM_024301.5(FKRP):c.447_451del (p.Ala150fs)	FKRP	Pathogenic	criteria provided, multiple submitters, no conflicts
2577157	NM_024301.5(FKRP):c.469G>C (p.Ala157Pro)	FKRP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2675695	NM_024301.5(FKRP):c.1336del (p.Leu446fs)	FKRP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2675696	NM_024301.5(FKRP):c.1000G>T (p.Glu334Ter)	FKRP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2675699	NM_024301.5(FKRP):c.938G>A (p.Trp313Ter)	FKRP	Pathogenic	criteria provided, single submitter
2675706	NM_024301.5(FKRP):c.217C>T (p.Gln73Ter)	FKRP	Pathogenic	criteria provided, multiple submitters, no conflicts
2675707	NM_024301.5(FKRP):c.1020C>G (p.Tyr340Ter)	FKRP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2675708	NM_024301.5(FKRP):c.1216C>T (p.Gln406Ter)	FKRP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2675709	NM_024301.5(FKRP):c.795_811del (p.Ala267fs)	FKRP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2732525	NM_024301.5(FKRP):c.265C>G (p.Pro89Ala)	FKRP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
282247	NM_024301.5(FKRP):c.545A>G (p.Tyr182Cys)	FKRP	Pathogenic	criteria provided, multiple submitters, no conflicts
282866	NM_024301.5(FKRP):c.162_165dup (p.Phe56fs)	FKRP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
284644	NM_024301.5(FKRP):c.313C>T (p.Gln105Ter)	FKRP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
289093	NM_024301.5(FKRP):c.1269_1270insT (p.Asn424Ter)	FKRP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
289096	NM_024301.5(FKRP):c.1267del (p.Arg423fs)	FKRP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2913953	NM_024301.5(FKRP):c.1208dup (p.Arg404fs)	FKRP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3241626	NM_024301.5(FKRP):c.1077G>A (p.Trp359Ter)	FKRP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4219	NM_024301.5(FKRP):c.1154C>A (p.Ser385Ter)	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
4226	NM_024301.5(FKRP):c.1364C>A (p.Ala455Asp)	FKRP	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 15 · 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
FKRP	Definitive	Autosomal recessive	autosomal recessive limb-girdle muscular dystrophy type 2I	15

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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

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
FKRP	HGNC:17997	ENSG00000181027	Q9H9S5	Ribitol 5-phosphate transferase FKRP	gencc,clinvar
STRN4	HGNC:15721	ENSG00000090372	Q9NRL3	Striatin-4	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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…
STRN4	Striatin-4	Calmodulin-binding scaffolding protein which is the center of the striatin-interacting phosphatase and kinase (STRIPAK) complexes.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 1 · Druggable fraction: 0.0

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
Scaffold/PPI	1	8.6×	0.225
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FKRP	Other/Unknown	no		LicD/FKTN/FKRP_NTP_transf, LicD_transferase, FKRP_N
STRN4	Scaffold/PPI	no		WD40_rpt, Striatin_N, WD40/YVTN_repeat-like_dom_sf

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
cardiac muscle of right atrium	1
hindlimb stylopod muscle	1
left ventricle myocardium	1
left testis	1
right testis	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FKRP	230	ubiquitous	marker	left ventricle myocardium, cardiac muscle of right atrium, hindlimb stylopod muscle
STRN4	232	ubiquitous	marker	left testis, right testis, sural nerve

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
STRN4	1,549
FKRP	1,436

Structural data

PDB: 1 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FKRP	Q9H9S5	8

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
STRN4	Q9NRL3	68.59

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 2 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	FKRP

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
pentitol metabolic process	1	8426.0×	0.002	FKRP
filtration diaphragm assembly	1	8426.0×	0.002	FKRP
pentose metabolic process	1	4213.0×	0.003	FKRP
creatine metabolic process	1	2106.5×	0.003	FKRP
connective tissue development	1	2106.5×	0.003	FKRP
oxygen metabolic process	1	2106.5×	0.003	FKRP
maintenance of protein localization in endoplasmic reticulum	1	1685.2×	0.003	FKRP
localization of cell	1	1404.3×	0.003	FKRP
connective tissue replacement	1	1203.7×	0.004	FKRP
diaphragm development	1	936.2×	0.004	FKRP
regulation of modification of postsynaptic structure	1	936.2×	0.004	STRN4
protein import	1	842.6×	0.004	FKRP
skeletal muscle fiber differentiation	1	842.6×	0.004	FKRP
response to alcohol	1	766.0×	0.004	FKRP
reelin-mediated signaling pathway	1	601.9×	0.004	FKRP
respiratory system process	1	468.1×	0.005	FKRP
protein O-linked glycosylation via mannose	1	468.1×	0.005	FKRP
glial cell differentiation	1	443.5×	0.005	FKRP
skeletal muscle tissue regeneration	1	443.5×	0.005	FKRP
negative regulation of hippo signaling	1	351.1×	0.006	STRN4
protein tetramerization	1	312.1×	0.006	FKRP
neuromuscular process	1	263.3×	0.007	FKRP
basement membrane organization	1	255.3×	0.007	FKRP
adult walking behavior	1	247.8×	0.007	FKRP
glycolytic process	1	191.5×	0.008	FKRP
heart morphogenesis	1	187.2×	0.008	FKRP
camera-type eye development	1	179.3×	0.008	FKRP
response to activity	1	162.0×	0.008	FKRP
response to glucocorticoid	1	162.0×	0.008	FKRP
bone mineralization	1	135.9×	0.010	FKRP

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
FKRP	0	0
STRN4	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	FKRP, STRN4

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)
FKRP	0	—
STRN4	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: FKRP, STRN4