autosomal recessive limb-girdle muscular dystrophy type 2L

Summary

autosomal recessive limb-girdle muscular dystrophy type 2L (MONDO:0012652) is a disease caused by ANO5 (GenCC Strong), with 1 cohort gene and 1 clinical trial.

At a glance

• Prevalence: Unknown (Worldwide) [Orphanet-validated]
• Causal gene: ANO5 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 1,163
• Phenotypes (HPO): 35
• Clinical trials: 1

Clinical features

Signs & symptoms

Clinical features (HPO)

35 HPO clinical features (Orphanet curated; top 35 by frequency):

HPO ID	Term	Frequency
HP:0003326	Myalgia	Very frequent (80-99%)
HP:0006785	Limb-girdle muscular dystrophy	Very frequent (80-99%)
HP:0008994	Proximal muscle weakness in lower limbs	Very frequent (80-99%)
HP:0009053	Distal lower limb muscle weakness	Very frequent (80-99%)
HP:0001430	Abnormality of the calf musculature	Frequent (30-79%)
HP:0002816	Genu recurvatum	Frequent (30-79%)
HP:0003236	Elevated circulating creatine kinase concentration	Frequent (30-79%)
HP:0003445	EMG: neuropathic changes	Frequent (30-79%)
HP:0003458	EMG: myopathic abnormalities	Frequent (30-79%)
HP:0003482	EMG: axonal abnormality	Frequent (30-79%)
HP:0003555	Muscle fiber splitting	Frequent (30-79%)
HP:0003557	Increased variability in muscle fiber diameter	Frequent (30-79%)
HP:0003730	EMG: myotonic runs	Frequent (30-79%)
HP:0003738	Exercise-induced myalgia	Frequent (30-79%)
HP:0004303	Abnormal muscle fiber morphology	Frequent (30-79%)
HP:0007210	Lower limb amyotrophy	Frequent (30-79%)
HP:0008988	Pelvic girdle muscle atrophy	Frequent (30-79%)
HP:0008997	Proximal muscle weakness in upper limbs	Frequent (30-79%)
HP:0009050	Quadriceps muscle atrophy	Frequent (30-79%)
HP:0012548	Fatty replacement of skeletal muscle	Frequent (30-79%)
HP:0031237	Internally nucleated skeletal muscle fibers	Frequent (30-79%)
HP:0100295	Muscle fiber atrophy	Frequent (30-79%)
HP:0100297	Increased endomysial connective tissue	Frequent (30-79%)
HP:0001638	Cardiomyopathy	Occasional (5-29%)
HP:0002913	Myoglobinuria	Occasional (5-29%)
HP:0002987	Elbow flexion contracture	Occasional (5-29%)
HP:0003089	Hamstring contractures	Occasional (5-29%)
HP:0003691	Scapular winging	Occasional (5-29%)
HP:0006466	Ankle flexion contracture	Occasional (5-29%)
HP:0008981	Calf muscle hypertrophy	Occasional (5-29%)
HP:0009129	Upper limb amyotrophy	Occasional (5-29%)
HP:0010628	Facial palsy	Occasional (5-29%)
HP:0012785	Flexion contracture of finger	Occasional (5-29%)
HP:0001239	Wrist flexion contracture	Occasional (5-29%)
HP:0001371	Flexion contracture	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal recessive limb-girdle muscular dystrophy type 2L
Mondo ID	MONDO:0012652
MeSH	C566968
OMIM	611307
Orphanet	206549
DOID	DOID:0110284
UMLS	C1969785
MedGen	370102
GARD	0012536
Is cancer (heuristic)	no

Also known as: ANO5 autosomal recessive limb-girdle muscular dystrophy · autosomal recessive limb-girdle muscular dystrophy caused by mutation in ANO5 · LGMD2L · limb-girdle muscular dystrophy type 2L · muscular dystrophy, limb-girdle, autosomal recessive 12 · muscular dystrophy, limb-girdle, type 2L

Data availability: 1,163 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › autosomal recessive limb-girdle muscular dystrophy › autosomal recessive limb-girdle muscular dystrophy type 2L

Related subtypes (31): epidermolysis bullosa simplex 5B, with muscular dystrophy, autosomal recessive limb-girdle muscular dystrophy type 2A, autosomal recessive limb-girdle muscular dystrophy type 2B, autosomal recessive limb-girdle muscular dystrophy type 2C, autosomal recessive limb-girdle muscular dystrophy type 2H, autosomal recessive limb-girdle muscular dystrophy type 2F, autosomal recessive limb-girdle muscular dystrophy type 2G, autosomal recessive limb-girdle muscular dystrophy type 2E, autosomal recessive limb-girdle muscular dystrophy type 2I, autosomal recessive limb-girdle muscular dystrophy type 2D, autosomal recessive limb-girdle muscular dystrophy type 2J, autosomal recessive limb-girdle muscular dystrophy type 2K, autosomal recessive limb-girdle muscular dystrophy type 2M, autosomal recessive limb-girdle muscular dystrophy type 2O, autosomal recessive limb-girdle muscular dystrophy type 2N, autosomal recessive limb-girdle muscular dystrophy type 2Q, autosomal recessive limb-girdle muscular dystrophy type 2P, autosomal recessive limb-girdle muscular dystrophy type 2T, autosomal recessive limb-girdle muscular dystrophy type R18, autosomal recessive limb-girdle muscular dystrophy type 2U, limb-girdle muscular dystrophy due to POMK deficiency, autosomal recessive limb-girdle muscular dystrophy type 2X, autosomal recessive limb-girdle muscular dystrophy type 2W, autosomal recessive limb-girdle muscular dystrophy type 2Y, autosomal recessive limb-girdle muscular dystrophy type 2R1, muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 8, muscular dystrophy, limb-girdle, autosomal recessive 23, muscular dystrophy, limb-girdle, autosomal recessive 26, muscular dystrophy, limb-girdle, autosomal recessive 27, muscular dystrophy, limb-girdle, autosomal recessive 28, muscular dystrophy, limb-girdle, autosomal recessive 29

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

600 retrieved; paginated sample, class counts are floors:

268 uncertain significance, 176 likely benign, 50 pathogenic, 48 conflicting classifications of pathogenicity, 23 likely pathogenic, 13 benign, 12 pathogenic/likely pathogenic, 10 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1008638	NC_000011.9:g.(?22242633)(22242766_?)del	ANO5	Pathogenic	criteria provided, single submitter
1066105	NC_000011.9:g.(?22276907)(22301321_?)del	ANO5	Pathogenic	criteria provided, single submitter
1073054	NM_213599.3(ANO5):c.1690C>T (p.Gln564Ter)	ANO5	Pathogenic	criteria provided, single submitter
1075891	NM_213599.3(ANO5):c.1924C>T (p.Arg642Ter)	ANO5	Pathogenic	criteria provided, single submitter
1076523	NM_213599.3(ANO5):c.823C>T (p.Gln275Ter)	ANO5	Pathogenic	criteria provided, single submitter
1323166	NM_213599.3(ANO5):c.1716C>A (p.Cys572Ter)	ANO5	Pathogenic	criteria provided, multiple submitters, no conflicts
1323234	NM_213599.3(ANO5):c.1086T>A (p.Tyr362Ter)	ANO5	Pathogenic	criteria provided, multiple submitters, no conflicts
1326848	NM_213599.3(ANO5):c.294+5G>A	ANO5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1350152	NC_000011.9:g.(?22242623)(22277088_?)del	ANO5	Pathogenic	criteria provided, single submitter
1358563	NM_213599.3(ANO5):c.1656T>G (p.Tyr552Ter)	ANO5	Pathogenic	criteria provided, single submitter
1374139	NM_213599.3(ANO5):c.773_774delinsAA (p.Trp258Ter)	ANO5	Pathogenic	criteria provided, single submitter
1380487	NM_213599.3(ANO5):c.766C>T (p.Gln256Ter)	ANO5	Pathogenic	criteria provided, single submitter
1382777	NM_213599.3(ANO5):c.1944_1945del (p.Lys650fs)	ANO5	Pathogenic	criteria provided, single submitter
1396797	NM_213599.3(ANO5):c.22G>T (p.Glu8Ter)	ANO5	Pathogenic	criteria provided, single submitter
140553	NM_213599.3(ANO5):c.1733T>C (p.Phe578Ser)	ANO5	Pathogenic	reviewed by expert panel
140555	NM_213599.3(ANO5):c.2018A>G (p.Tyr673Cys)	ANO5	Pathogenic	reviewed by expert panel
1406379	NM_213599.3(ANO5):c.1222del (p.Leu408fs)	ANO5	Pathogenic	criteria provided, single submitter
1432460	NC_000011.9:g.(?22225330)(22225416_?)del	ANO5	Pathogenic	criteria provided, single submitter
1440062	NM_213599.3(ANO5):c.2193_2197del (p.Gln731fs)	ANO5	Pathogenic	criteria provided, single submitter
1452790	NM_213599.3(ANO5):c.1531C>T (p.Gln511Ter)	ANO5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1453293	NM_213599.3(ANO5):c.1045C>T (p.Gln349Ter)	ANO5	Pathogenic	criteria provided, single submitter
1454753	NC_000011.9:g.(?22261105)(22301321_?)del	ANO5	Pathogenic	criteria provided, single submitter
1455578	NM_213599.3(ANO5):c.989T>A (p.Leu330Ter)	ANO5	Pathogenic	criteria provided, single submitter
1457293	NC_000011.9:g.(?22281045)(22281307_?)del	ANO5	Pathogenic	criteria provided, single submitter
1457294	NC_000011.9:g.(?22215039)(22247618_?)del	ANO5	Pathogenic	criteria provided, single submitter
1457296	NC_000011.9:g.(?22242623)(22301311_?)del	ANO5	Pathogenic	criteria provided, single submitter
1457438	NM_213599.3(ANO5):c.258C>A (p.Tyr86Ter)	ANO5	Pathogenic	criteria provided, multiple submitters, no conflicts
1459484	NC_000011.9:g.(?22215039)(22225416_?)del	ANO5	Pathogenic	criteria provided, single submitter
1460312	NM_213599.3(ANO5):c.738C>G (p.Tyr246Ter)	ANO5	Pathogenic	criteria provided, single submitter
1906545	NM_213599.3(ANO5):c.1794_1798dup (p.Glu600fs)	ANO5	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 10 · Orphanet: 5 · 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
ANO5	Strong	Autosomal recessive	autosomal recessive limb-girdle muscular dystrophy type 2L	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ANO5	Orphanet:206549	Anoctamin-5-related limb-girdle muscular dystrophy R12
ANO5	Orphanet:206599	Isolated asymptomatic elevation of creatine phosphokinase
ANO5	Orphanet:399096	Distal anoctaminopathy
ANO5	Orphanet:53697	Gnathodiaphyseal dysplasia
ANO5	Orphanet:689021	Asymptomatic hyperCKemia-myalgia-rhabdomyolysis 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
ANO5	HGNC:27337	ENSG00000171714	Q75V66	Anoctamin-5	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ANO5	Anoctamin-5	Plays a role in plasma membrane repair in a process involving annexins.

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)
ANO5	Other/Unknown	no		Anoctamin, Anoct_dimer, Anoctamin_TM

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
left ventricle myocardium	1
vastus lateralis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ANO5	220	broad	marker	cardiac muscle of right atrium, left ventricle myocardium, vastus lateralis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ANO5	790

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ANO5	Q75V66	82.22

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. 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
Induction of Cell-Cell Fusion	1	878.5×	0.013	ANO5
Late SARS-CoV-2 Infection Events	1	292.8×	0.016	ANO5
Regulation of clotting cascade	1	233.1×	0.016	ANO5
Stimuli-sensing channels	1	135.9×	0.020	ANO5
Ion channel transport	1	96.0×	0.023	ANO5
SARS-CoV-2 Infection	1	80.4×	0.023	ANO5
SARS-CoV Infections	1	55.4×	0.028	ANO5
Viral Infection Pathways	1	30.8×	0.044	ANO5
Transport of small molecules	1	25.1×	0.044	ANO5
Infectious disease	1	24.8×	0.044	ANO5
Disease	1	13.1×	0.076	ANO5

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
plasma membrane repair	1	581.1×	0.005	ANO5
chloride transmembrane transport	1	237.3×	0.005	ANO5
monoatomic ion transmembrane transport	1	208.1×	0.005	ANO5

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
ANO5	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	ANO5

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)
ANO5	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