Muscular dystrophy, limb-girdle, autosomal recessive 26

Summary

Muscular dystrophy, limb-girdle, autosomal recessive 26 (MONDO:0030014) is a disease caused by POPDC3 (GenCC Strong), with 2 cohort genes.

At a glance

• Causal gene: POPDC3 (GenCC Strong)
• Cohort genes: 2
• ClinVar variants: 7

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	muscular dystrophy, limb-girdle, autosomal recessive 26
Mondo ID	MONDO:0030014
OMIM	618848
DOID	DOID:0061131
UMLS	C5394268
MedGen	1718449
GARD	0025507
Is cancer (heuristic)	no

Also known as: LGMDR26 · MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 26 · muscular dystrophy, limb-girdle, autosomal recessive 26

Data availability: 7 ClinVar variants · 3 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 › muscular dystrophy, limb-girdle, autosomal recessive 26

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 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 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

7 retrieved; paginated sample, class counts are floors:

6 pathogenic, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
869186	NM_022361.5(POPDC3):c.782G>A (p.Arg261Gln)	BVES-AS1	Pathogenic	no assertion criteria provided
869187	NM_022361.5(POPDC3):c.464T>A (p.Leu155His)	BVES-AS1	Pathogenic	no assertion criteria provided
869188	NM_022361.5(POPDC3):c.651A>T (p.Leu217Phe)	BVES-AS1	Pathogenic	no assertion criteria provided
3069143	NM_022361.5(POPDC3):c.460A>G (p.Lys154Glu)	POPDC1-AS1	Pathogenic	no assertion criteria provided
3069144	NM_022361.5(POPDC3):c.486-1G>A	POPDC1-AS1	Pathogenic	no assertion criteria provided
3069145	NM_022361.5(POPDC3):c.486-6T>A	POPDC1-AS1	Pathogenic	no assertion criteria provided
3896961	NM_022361.5(POPDC3):c.316C>T (p.Arg106Ter)	POPDC1-AS1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 0 · 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
POPDC3	Strong	Autosomal recessive	muscular dystrophy, limb-girdle, autosomal recessive 26	3

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
POPDC3	HGNC:17649	ENSG00000132429	Q9HBV1	Popeye domain-containing protein 3	gencc
POPDC1-AS1	HGNC:21223	ENSG00000203808	Q5T3Y7	Putative uncharacterized protein POPDC1-AS1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
POPDC3	Popeye domain-containing protein 3	May play a role in the maintenance of heart function mediated, at least in part, through cAMP-binding.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
POPDC3	Other/Unknown	no		POPDC1-3, cNMP-bd_dom_sf, POPDC1-3_dom
POPDC1-AS1	Other/Unknown	no

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
biceps brachii	1
hindlimb stylopod muscle	1
skeletal muscle tissue of rectus abdominis	1
gastrocnemius	1
male germ line stem cell (sensu Vertebrata) in testis	1
sperm	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
POPDC3	218	ubiquitous	marker	skeletal muscle tissue of rectus abdominis, biceps brachii, hindlimb stylopod muscle
POPDC1-AS1	161	broad	yes	gastrocnemius, male germ line stem cell (sensu Vertebrata) in testis, sperm

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
POPDC3	549
POPDC1-AS1	0

Structural data

PDB: 0 · AlphaFold-only: 2 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
POPDC3	Q9HBV1	81.87
POPDC1-AS1	Q5T3Y7	41.85

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 2 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
striated muscle cell differentiation	1	991.3×	0.004	POPDC3
skeletal muscle tissue development	1	290.6×	0.006	POPDC3
regulation of membrane potential	1	230.8×	0.006	POPDC3
heart development	1	78.8×	0.013	POPDC3

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
POPDC3	0	0
POPDC1-AS1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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	0
E	Difficult family or no structure, no drug	2	POPDC3, POPDC1-AS1

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)
POPDC3	0	—
POPDC1-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.