muscular dystrophy-dystroglycanopathy type B5

Summary

muscular dystrophy-dystroglycanopathy type B5 (MONDO:0011688) is a disease caused by FKRP (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: FKRP (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 119

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	muscular dystrophy-dystroglycanopathy type B5
Mondo ID	MONDO:0011688
MeSH	C564691
OMIM	606612
Orphanet	52428
DOID	DOID:0110635
UMLS	C1847759
MedGen	335764
GARD	0024818
Is cancer (heuristic)	no

Also known as: congenital muscular dystrophy-FKRP related · MDC1C · MDDGB5 · muscular dystrophy-dystroglycanopathy (congenital with or without intellectual disability), type B, 5 · muscular dystrophy-dystroglycanopathy (congenital with or without mental retardation), type B, 5

Data availability: 119 ClinVar variants · 2 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 B › muscular dystrophy-dystroglycanopathy type B5

Related subtypes (7): muscular dystrophy-dystroglycanopathy type B6, muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B3, muscular dystrophy-dystroglycanopathy (congenital without intellectual disability), type B4, muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1, muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B2, muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B14, muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 15

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

119 retrieved; paginated sample, class counts are floors:

48 uncertain significance, 23 conflicting classifications of pathogenicity, 19 pathogenic/likely pathogenic, 13 likely pathogenic, 5 benign/likely benign, 5 pathogenic, 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
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
197347	NM_024301.5(FKRP):c.947C>G (p.Pro316Arg)	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
289473	NM_024301.5(FKRP):c.970G>T (p.Glu324Ter)	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
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
4224	NM_024301.5(FKRP):c.946C>A (p.Pro316Thr)	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
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
553930	NM_024301.5(FKRP):c.1012G>T (p.Val338Leu)	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
930906	NM_024301.5(FKRP):c.962C>A (p.Ala321Glu)	FKRP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
939991	NM_024301.5(FKRP):c.206_208del (p.Ser69del)	FKRP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
96115	NM_024301.5(FKRP):c.941C>T (p.Thr314Met)	FKRP	Pathogenic	criteria provided, multiple submitters, no conflicts
1334893	NM_024301.5(FKRP):c.503G>A (p.Cys168Tyr)	FKRP	Likely pathogenic	criteria provided, single submitter
3584041	NM_024301.5(FKRP):c.2T>C (p.Met1Thr)	FKRP	Likely pathogenic	criteria provided, single submitter
3584042	NM_024301.5(FKRP):c.265C>T (p.Pro89Ser)	FKRP	Likely pathogenic	criteria provided, single submitter
3584043	NM_024301.5(FKRP):c.884_885del (p.Arg295fs)	FKRP	Likely pathogenic	criteria provided, single submitter
3584044	NM_024301.5(FKRP):c.899T>A (p.Val300Glu)	FKRP	Likely pathogenic	criteria provided, single submitter
3584045	NM_024301.5(FKRP):c.927C>A (p.Tyr309Ter)	FKRP	Likely pathogenic	criteria provided, single submitter

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

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
FKRP	HGNC:17997	ENSG00000181027	Q9H9S5	Ribitol 5-phosphate transferase FKRP	gencc,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…

Protein-family classification

Druggable: 0 · Difficult: 0 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FKRP	Other/Unknown	no		LicD/FKTN/FKRP_NTP_transf, LicD_transferase, FKRP_N

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
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
FKRP	230	ubiquitous	marker	left ventricle myocardium, cardiac muscle of right atrium, hindlimb stylopod muscle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FKRP	1,436

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FKRP	Q9H9S5	8

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 1 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 1 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	16852.0×	0.001	FKRP
filtration diaphragm assembly	1	16852.0×	0.001	FKRP
pentose metabolic process	1	8426.0×	0.001	FKRP
creatine metabolic process	1	4213.0×	0.001	FKRP
connective tissue development	1	4213.0×	0.001	FKRP
oxygen metabolic process	1	4213.0×	0.001	FKRP
maintenance of protein localization in endoplasmic reticulum	1	3370.4×	0.002	FKRP
localization of cell	1	2808.7×	0.002	FKRP
connective tissue replacement	1	2407.4×	0.002	FKRP
diaphragm development	1	1872.4×	0.002	FKRP
protein import	1	1685.2×	0.002	FKRP
skeletal muscle fiber differentiation	1	1685.2×	0.002	FKRP
response to alcohol	1	1532.0×	0.002	FKRP
reelin-mediated signaling pathway	1	1203.7×	0.002	FKRP
respiratory system process	1	936.2×	0.002	FKRP
protein O-linked glycosylation via mannose	1	936.2×	0.002	FKRP
glial cell differentiation	1	887.0×	0.002	FKRP
skeletal muscle tissue regeneration	1	887.0×	0.002	FKRP
protein tetramerization	1	624.1×	0.003	FKRP
neuromuscular process	1	526.6×	0.003	FKRP
basement membrane organization	1	510.7×	0.003	FKRP
adult walking behavior	1	495.6×	0.003	FKRP
glycolytic process	1	383.0×	0.004	FKRP
heart morphogenesis	1	374.5×	0.004	FKRP
camera-type eye development	1	358.6×	0.004	FKRP
response to activity	1	324.1×	0.004	FKRP
response to glucocorticoid	1	324.1×	0.004	FKRP
bone mineralization	1	271.8×	0.005	FKRP
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	210.7×	0.006	FKRP
muscle contraction	1	208.1×	0.006	FKRP

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 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

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; 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	1	FKRP

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
FKRP	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.