Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 10

disease

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Also known as MDDGA10muscular dystrophy-dystroglycanopathy, type A caused by mutation in RXYLT1RXYLT1 muscular dystrophy-dystroglycanopathy, type A

Summary

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 10 (MONDO:0014022) is a disease caused by RXYLT1 (GenCC Definitive), with 2 cohort genes.

At a glance

Causal gene: RXYLT1 (GenCC Definitive)
Cohort genes: 2
ClinVar variants: 36

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, 10
Mondo ID	MONDO:0014022
OMIM	615041
DOID	DOID:0111239
UMLS	C3554381
MedGen	767295
GARD	0015898
Is cancer (heuristic)	no

Also known as: MDDGA10 · muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 10 · muscular dystrophy-dystroglycanopathy, type A caused by mutation in RXYLT1 · RXYLT1 muscular dystrophy-dystroglycanopathy, type A

Data availability: 36 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, 10

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

36 retrieved; paginated sample, class counts are floors:

16 uncertain significance, 7 pathogenic/likely pathogenic, 5 pathogenic, 4 conflicting classifications of pathogenicity, 2 likely pathogenic, 1 benign, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1686135	NM_014254.3(RXYLT1):c.429-2A>G	RXYLT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1704385	NM_014254.3(RXYLT1):c.169+2T>C	RXYLT1	Pathogenic	criteria provided, single submitter
265345	NM_014254.3(RXYLT1):c.92del (p.Arg31fs)	RXYLT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2780252	NM_014254.3(RXYLT1):c.389G>A (p.Trp130Ter)	RXYLT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
39603	NM_014254.3(RXYLT1):c.795del (p.Arg266fs)	RXYLT1	Pathogenic	criteria provided, single submitter
39604	NM_014254.3(RXYLT1):c.1016A>G (p.Tyr339Cys)	RXYLT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
39606	NM_014254.3(RXYLT1):c.1064_1091del (p.Asp355fs)	RXYLT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
39607	NM_014254.3(RXYLT1):c.279del (p.Gly94fs)	RXYLT1	Pathogenic	no assertion criteria provided
50606	NM_014254.3(RXYLT1):c.1018C>T (p.Arg340Ter)	RXYLT1	Pathogenic	criteria provided, multiple submitters, no conflicts
50607	NM_014254.3(RXYLT1):c.139del (p.Ala47fs)	RXYLT1	Pathogenic	criteria provided, multiple submitters, no conflicts
634990	NM_014254.3(RXYLT1):c.390G>A (p.Trp130Ter)	RXYLT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
854859	NM_014254.3(RXYLT1):c.997G>A (p.Gly333Arg)	RXYLT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1704388	NM_014254.3(RXYLT1):c.1024del (p.Tyr342fs)	RXYLT1	Likely pathogenic	criteria provided, single submitter
963083	NM_014254.3(RXYLT1):c.325+1G>T	RXYLT1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
430845	NM_024301.5(FKRP):c.679G>C (p.Ala227Pro)	FKRP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1587287	NM_014254.3(RXYLT1):c.170-17_170-14del	RXYLT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
429848	NM_014254.3(RXYLT1):c.914+6T>G	RXYLT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
639854	NM_014254.3(RXYLT1):c.604G>A (p.Gly202Arg)	RXYLT1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1032614	NM_014254.3(RXYLT1):c.92G>T (p.Arg31Leu)	RXYLT1	Uncertain significance	criteria provided, single submitter
1805579	NM_014254.3(RXYLT1):c.539G>T (p.Trp180Leu)	RXYLT1	Uncertain significance	criteria provided, single submitter
2081258	NM_014254.3(RXYLT1):c.233A>G (p.Gln78Arg)	RXYLT1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2435495	NM_014254.3(RXYLT1):c.992C>T (p.Pro331Leu)	RXYLT1	Uncertain significance	criteria provided, multiple submitters, no conflicts
3242184	NM_014254.3(RXYLT1):c.760G>A (p.Val254Met)	RXYLT1	Uncertain significance	criteria provided, single submitter
39605	NM_014254.3(RXYLT1):c.1019_1020delinsTT (p.Arg340Leu)	RXYLT1	Uncertain significance	criteria provided, single submitter
4079904	NM_014254.3(RXYLT1):c.-3G>A	RXYLT1	Uncertain significance	criteria provided, single submitter
4079905	NM_014254.3(RXYLT1):c.1204A>G (p.Ile402Val)	RXYLT1	Uncertain significance	criteria provided, single submitter
4079906	NM_014254.3(RXYLT1):c.1129A>G (p.Lys377Glu)	RXYLT1	Uncertain significance	criteria provided, single submitter
4079907	NM_014254.3(RXYLT1):c.914A>G (p.His305Arg)	RXYLT1	Uncertain significance	criteria provided, single submitter
473414	NM_014254.3(RXYLT1):c.237C>G (p.His79Gln)	RXYLT1	Uncertain significance	criteria provided, multiple submitters, no conflicts
473417	NM_014254.3(RXYLT1):c.920A>G (p.Gln307Arg)	RXYLT1	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 7 · 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
RXYLT1	Definitive	Autosomal recessive	muscle-eye-brain disease	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RXYLT1	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

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
RXYLT1	HGNC:13530	ENSG00000118600	Q9Y2B1	Ribitol-5-phosphate xylosyltransferase 1	gencc,clinvar
FKRP	HGNC:17997	ENSG00000181027	Q9H9S5	Ribitol 5-phosphate transferase FKRP	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RXYLT1	Ribitol-5-phosphate xylosyltransferase 1	Acts as a UDP-D-xylose:ribitol-5-phosphate beta1,4-xylosyltransferase, which catalyzes the transfer of UDP-D-xylose to ribitol 5-phosphate (Rbo5P) to form the Xylbeta1-4Rbo5P linkage on O-mannosyl glycan.
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…

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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	6.0×	0.320
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RXYLT1	Enzyme (other)	yes	2.4.2.61	RXYLT1-like, RXYLT1_C, RXYLT1_N
FKRP	Other/Unknown	no		LicD/FKTN/FKRP_NTP_transf, LicD_transferase, FKRP_N

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
caput epididymis	1
corpus epididymis	1
cranial nerve II	1
cardiac muscle of right atrium	1
hindlimb stylopod muscle	1
left ventricle myocardium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RXYLT1	293	ubiquitous	marker	corpus epididymis, caput epididymis, cranial nerve II
FKRP	230	ubiquitous	marker	left ventricle myocardium, cardiac muscle of right atrium, hindlimb stylopod muscle

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FKRP	1,436
RXYLT1	675

Intra-cohort edges

A	B	Sources
FKRP	RXYLT1	intact, string_interaction

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
RXYLT1	Q9Y2B1	85.72

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 2 evidence-associated genes (2 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 2 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	2	815.7×	1e-06	RXYLT1, FKRP

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
protein O-linked glycosylation via mannose	2	936.2×	4e-05	RXYLT1, FKRP
pentitol metabolic process	1	8426.0×	0.002	FKRP
filtration diaphragm assembly	1	8426.0×	0.002	FKRP
pentose metabolic process	1	4213.0×	0.002	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×	0.003	FKRP
diaphragm development	1	936.2×	0.003	FKRP
protein import	1	842.6×	0.003	FKRP
skeletal muscle fiber differentiation	1	842.6×	0.003	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
glial cell differentiation	1	443.5×	0.005	FKRP
skeletal muscle tissue regeneration	1	443.5×	0.005	FKRP
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×	0.009	FKRP
response to glucocorticoid	1	162.0×	0.009	FKRP
bone mineralization	1	135.9×	0.010	FKRP
protein O-linked glycosylation	1	112.3×	0.012	RXYLT1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	105.3×	0.012	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
RXYLT1	0	0
FKRP	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
RXYLT1	2.4.2.61	alpha-dystroglycan beta1,4-xylosyltransferase

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	1	RXYLT1
E	Difficult family or no structure, no drug	1	FKRP

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)
RXYLT1	0	—
FKRP	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: RXYLT1, FKRP