autosomal recessive limb-girdle muscular dystrophy type 2M

Summary

autosomal recessive limb-girdle muscular dystrophy type 2M (MONDO:0012699) is a disease caused by FKTN (GenCC Definitive), with 1 cohort gene and 1 clinical trial.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: FKTN (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 113
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		5	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal recessive limb-girdle muscular dystrophy type 2M
Mondo ID	MONDO:0012699
MeSH	C566912
OMIM	611588
Orphanet	206554
DOID	DOID:0110296
UMLS	C1969040
MedGen	370585
GARD	0012538
Is cancer (heuristic)	no

Also known as: autosomal recessive limb-girdle muscular dystrophy caused by mutation in FKTN · FKTN autosomal recessive limb-girdle muscular dystrophy · LGMD-FKTN related · LGMD2M · limb-girdle muscular dystrophy type 2M · MDDGC4 · muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 4

Data availability: 113 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 C › autosomal recessive limb-girdle muscular dystrophy type 2M

Related subtypes (8): autosomal recessive limb-girdle muscular dystrophy type 2K, autosomal recessive limb-girdle muscular dystrophy type 2O, autosomal recessive limb-girdle muscular dystrophy type 2N, autosomal recessive limb-girdle muscular dystrophy type 2P, autosomal recessive limb-girdle muscular dystrophy type 2T, autosomal recessive limb-girdle muscular dystrophy type 2U, limb-girdle muscular dystrophy due to POMK deficiency, muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 8

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

113 retrieved; paginated sample, class counts are floors:

46 uncertain significance, 27 likely pathogenic, 18 conflicting classifications of pathogenicity, 13 pathogenic/likely pathogenic, 3 likely benign, 3 benign/likely benign, 3 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
167069	NM_001079802.2(FKTN):c.411C>A (p.Cys137Ter)	FKTN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1970586	NM_001079802.2(FKTN):c.164G>A (p.Trp55Ter)	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
3208	NM_001079802.2(FKTN):c.920G>A (p.Arg307Gln)	FKTN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3216	NM_001079802.2(FKTN):c.919C>T (p.Arg307Ter)	FKTN	Pathogenic	criteria provided, multiple submitters, no conflicts
3596214	NM_001079802.2(FKTN):c.1045-6C>G	FKTN	Pathogenic	criteria provided, multiple submitters, no conflicts
370768	NM_001079802.2(FKTN):c.109G>T (p.Gly37Ter)	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
596647	NM_001079802.2(FKTN):c.369+1G>C	FKTN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
654926	NM_001079802.2(FKTN):c.1261_1286delinsACC (p.Ala421fs)	FKTN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
844703	NM_001079802.2(FKTN):c.329_330del (p.Phe110fs)	FKTN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
93523	NM_001079802.2(FKTN):c.642dup (p.Asp215Ter)	FKTN	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1724541	NM_001079802.2(FKTN):c.400G>T (p.Gly134Ter)	FKTN	Likely pathogenic	criteria provided, single submitter
1724610	NM_001079802.2(FKTN):c.569_570del (p.Arg190fs)	FKTN	Likely pathogenic	criteria provided, single submitter
1724752	NM_001079802.2(FKTN):c.436dup (p.Arg146fs)	FKTN	Likely pathogenic	criteria provided, single submitter
1724953	NM_001079802.2(FKTN):c.428_429delinsT (p.Lys143fs)	FKTN	Likely pathogenic	criteria provided, single submitter
1725035	NM_001079802.2(FKTN):c.442_443del (p.Asp148fs)	FKTN	Likely pathogenic	criteria provided, single submitter
1725272	NM_001079802.2(FKTN):c.970_973delinsTT (p.Ile324fs)	FKTN	Likely pathogenic	criteria provided, single submitter
1725583	NM_001079802.2(FKTN):c.378del (p.Trp126fs)	FKTN	Likely pathogenic	criteria provided, single submitter
1725624	NM_001079802.2(FKTN):c.745_746delinsT (p.Glu249fs)	FKTN	Likely pathogenic	criteria provided, single submitter
1726110	NM_001079802.2(FKTN):c.587_590del (p.Asp196fs)	FKTN	Likely pathogenic	criteria provided, single submitter
1726685	NM_001079802.2(FKTN):c.245T>A (p.Leu82Ter)	FKTN	Likely pathogenic	criteria provided, single submitter
1726869	NM_001079802.2(FKTN):c.69dup (p.Gln24fs)	FKTN	Likely pathogenic	criteria provided, single submitter
1726984	NM_001079802.2(FKTN):c.840dup (p.Leu281fs)	FKTN	Likely pathogenic	criteria provided, single submitter
2675716	NM_001079802.2(FKTN):c.49A>C (p.Ser17Arg)	FKTN	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3207	NM_001079802.2(FKTN):c.1363del (p.Asp455fs)	FKTN	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 13 · 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
FKTN	Definitive	Autosomal recessive	muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4	13

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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

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
FKTN	HGNC:3622	ENSG00000106692	O75072	Ribitol-5-phosphate transferase FKTN	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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…

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)
FKTN	Other/Unknown	no		LicD/FKTN/FKRP_NTP_transf, FKTN/MNN-like, FKTN_N

Expression context

Cohort genes with no expression data: 0.

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
adrenal tissue	1
calcaneal tendon	1
germinal epithelium of ovary	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FKTN	277	ubiquitous	yes	calcaneal tendon, adrenal tissue, germinal epithelium of ovary

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FKTN	1,226

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FKTN	O75072	92.48

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	FKTN

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
cerebellar cortex development	1	2106.5×	0.003	FKTN
skeletal muscle fiber differentiation	1	1685.2×	0.003	FKTN
protein O-linked glycosylation via mannose	1	936.2×	0.004	FKTN
negative regulation of JNK cascade	1	561.7×	0.004	FKTN
basement membrane organization	1	510.7×	0.004	FKTN
protein O-linked glycosylation	1	224.7×	0.007	FKTN
cerebral cortex development	1	205.5×	0.007	FKTN
muscle organ development	1	166.8×	0.007	FKTN
nervous system development	1	45.9×	0.024	FKTN
negative regulation of cell population proliferation	1	42.1×	0.024	FKTN

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
FKTN	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	FKTN

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)
FKTN	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05989620	Not specified	RECRUITING	Long-Term Development of Muscular Dystrophy Outcome Assessments