autosomal recessive limb-girdle muscular dystrophy type 2X

Summary

autosomal recessive limb-girdle muscular dystrophy type 2X (MONDO:0014782) is a disease caused by POPDC1 (GenCC Strong), with 1 cohort gene and 1 clinical trial.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: POPDC1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 43
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		3	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal recessive limb-girdle muscular dystrophy type 2X
Mondo ID	MONDO:0014782
OMIM	616812
Orphanet	476084
DOID	DOID:0110290
UMLS	C5568138
MedGen	1799561
GARD	0017847
Is cancer (heuristic)	no

Also known as: autosomal recessive limb-girdle muscular dystrophy caused by mutation in BVES · autosomal recessive limb-girdle muscular dystrophy-cardiac arrhythmia syndrome · BVES autosomal recessive limb-girdle muscular dystrophy · LGMD2X · muscular dystrophy, limb-girdle, autosomal recessive 25 · muscular dystrophy, limb-girdle, type 2X · muscular dystrophy, limb-girdle, type 2x

Data availability: 43 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 2X

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 2L, 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 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

43 retrieved; paginated sample, class counts are floors:

30 uncertain significance, 4 likely pathogenic, 3 benign, 3 pathogenic, 1 pathogenic/likely pathogenic, 1 conflicting classifications of pathogenicity, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1702994	NM_001199563.2(BVES):c.578T>G (p.Ile193Ser)	BVES	Pathogenic	no assertion criteria provided
626313	NM_001199563.2(BVES):c.816+2T>C	BVES	Pathogenic	no assertion criteria provided
626315	NM_001199563.2(BVES):c.1A>G (p.Met1Val)	BVES	Pathogenic	no assertion criteria provided
626314	NM_001199563.2(POPDC1):c.262C>T (p.Arg88Ter)	POPDC1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1723441	NM_001199563.2(POPDC1):c.518dup (p.Ser174fs)	POPDC1	Likely pathogenic	criteria provided, single submitter
222033	NM_001199563.2(POPDC1):c.602C>T (p.Ser201Phe)	POPDC1	Likely pathogenic	criteria provided, multiple submitters, no conflicts
4081212	NM_001199563.2(POPDC1):c.351+1del	POPDC1	Likely pathogenic	criteria provided, single submitter
624258	NM_001199563.2(POPDC1):c.457C>T (p.Gln153Ter)	POPDC1	Likely pathogenic	criteria provided, single submitter
731903	NM_001199563.2(POPDC1):c.574A>G (p.Asn192Asp)	POPDC1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1203460	NM_001199563.2(POPDC1):c.910G>A (p.Asp304Asn)	POPDC1	Uncertain significance	criteria provided, multiple submitters, no conflicts
1307192	NM_001199563.2(POPDC1):c.836A>G (p.His279Arg)	POPDC1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2352385	NM_001199563.2(POPDC1):c.386G>A (p.Arg129Gln)	POPDC1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2439584	NM_001199563.2(POPDC1):c.572A>G (p.His191Arg)	POPDC1	Uncertain significance	criteria provided, single submitter
2439585	NM_001199563.2(POPDC1):c.515G>A (p.Arg172His)	POPDC1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2439586	NM_001199563.2(POPDC1):c.807A>T (p.Leu269Phe)	POPDC1	Uncertain significance	criteria provided, single submitter
2439587	NM_001199563.2(POPDC1):c.74T>C (p.Ile25Thr)	POPDC1	Uncertain significance	criteria provided, single submitter
2439588	NM_001199563.2(POPDC1):c.938_939insT (p.Ser314fs)	POPDC1	Uncertain significance	criteria provided, single submitter
2439589	NM_001199563.2(POPDC1):c.263G>A (p.Arg88Gln)	POPDC1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2439590	NM_001199563.2(POPDC1):c.244G>A (p.Val82Ile)	POPDC1	Uncertain significance	criteria provided, single submitter
2439591	NM_001199563.2(POPDC1):c.758T>C (p.Ile253Thr)	POPDC1	Uncertain significance	criteria provided, single submitter
2439592	NM_001199563.2(POPDC1):c.1073A>G (p.Gln358Arg)	POPDC1	Uncertain significance	criteria provided, single submitter
2439593	NM_001199563.2(POPDC1):c.938C>T (p.Thr313Ile)	POPDC1	Uncertain significance	criteria provided, single submitter
2439594	NM_001199563.2(POPDC1):c.771C>G (p.Ile257Met)	POPDC1	Uncertain significance	criteria provided, single submitter
2439596	NM_001199563.2(POPDC1):c.1033G>A (p.Val345Ile)	POPDC1	Uncertain significance	criteria provided, single submitter
2439597	NM_001199563.2(POPDC1):c.569T>C (p.Leu190Pro)	POPDC1	Uncertain significance	criteria provided, single submitter
2439598	NM_001199563.2(POPDC1):c.184C>G (p.Leu62Val)	POPDC1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2439599	NM_001199563.2(POPDC1):c.64G>C (p.Glu22Gln)	POPDC1	Uncertain significance	criteria provided, single submitter
2439600	NM_001199563.2(POPDC1):c.876G>A (p.Met292Ile)	POPDC1	Uncertain significance	criteria provided, single submitter
2439601	NM_001199563.2(POPDC1):c.841C>G (p.Leu281Val)	POPDC1	Uncertain significance	criteria provided, single submitter
2439602	NM_001199563.2(POPDC1):c.932G>A (p.Arg311Gln)	POPDC1	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · 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
POPDC1	Strong	Autosomal recessive	autosomal recessive limb-girdle muscular dystrophy type 2X	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
POPDC1	Orphanet:476084	BVES-related limb-girdle muscular dystrophy

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
POPDC1	HGNC:1152	ENSG00000112276	Q8NE79	Popeye domain-containing protein 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
POPDC1	Popeye domain-containing protein 1	Cell adhesion molecule involved in the establishment and/or maintenance of cell integrity.

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)
POPDC1	Other/Unknown	no		POPDC1-3, RmlC-like_jellyroll, cNMP-bd_dom_sf

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
cardiac muscle of right atrium	1
left ventricle myocardium	1
tibialis anterior	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
POPDC1	211	ubiquitous	yes	left ventricle myocardium, tibialis anterior, cardiac muscle of right atrium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
POPDC1	628

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
POPDC1	Q8NE79	76.08

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

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
positive regulation of locomotion	1	5617.3×	0.002	POPDC1
cell migration involved in heart development	1	5617.3×	0.002	POPDC1
sinoatrial node cell development	1	2808.7×	0.002	POPDC1
regulation of endocytic recycling	1	1685.2×	0.003	POPDC1
epithelial cell-cell adhesion	1	1203.7×	0.003	POPDC1
positive regulation of receptor recycling	1	1123.5×	0.003	POPDC1
striated muscle cell differentiation	1	991.3×	0.003	POPDC1
obsolete vesicle docking	1	766.0×	0.003	POPDC1
regulation of GTPase activity	1	510.7×	0.004	POPDC1
regulation of heart rate	1	468.1×	0.004	POPDC1
substrate adhesion-dependent cell spreading	1	343.9×	0.005	POPDC1
skeletal muscle tissue development	1	290.6×	0.005	POPDC1
response to ischemia	1	251.5×	0.005	POPDC1
hematopoietic progenitor cell differentiation	1	237.3×	0.005	POPDC1
regulation of membrane potential	1	230.8×	0.005	POPDC1
muscle organ development	1	166.8×	0.007	POPDC1
regulation of cell shape	1	123.0×	0.009	POPDC1
vesicle-mediated transport	1	96.3×	0.011	POPDC1
heart development	1	78.8×	0.013	POPDC1

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
POPDC1	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	POPDC1

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)
POPDC1	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