autosomal recessive limb-girdle muscular dystrophy type 2O

Summary

autosomal recessive limb-girdle muscular dystrophy type 2O (MONDO:0013161) is a disease caused by POMGNT1 (GenCC Definitive), with 3 cohort genes and 1 clinical trial.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: POMGNT1 (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 1,213
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		2	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal recessive limb-girdle muscular dystrophy type 2O
Mondo ID	MONDO:0013161
OMIM	613157
Orphanet	206564
DOID	DOID:0110292
UMLS	C3150417
MedGen	461767
GARD	0012540
Is cancer (heuristic)	no

Also known as: autosomal recessive limb-girdle muscular dystrophy caused by mutation in POMGNT1 · LGMD-POMGNT1 related · LGMD2O · limb-girdle muscular dystrophy type 2O · MDDGC3 · muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 3 · POMGNT1 autosomal recessive limb-girdle muscular dystrophy

Data availability: 1,213 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 2O

Related subtypes (8): autosomal recessive limb-girdle muscular dystrophy type 2K, autosomal recessive limb-girdle muscular dystrophy type 2M, 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

600 retrieved; paginated sample, class counts are floors:

307 likely benign, 206 uncertain significance, 26 pathogenic, 24 conflicting classifications of pathogenicity, 16 likely pathogenic, 14 pathogenic/likely pathogenic, 5 benign, 2 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1459647	NC_000001.10:g.(?46662483)(46671639_?)del	LURAP1	Pathogenic	criteria provided, single submitter
1076645	NM_017739.4(POMGNT1):c.1545del (p.Tyr516fs)	POMGNT1	Pathogenic	criteria provided, multiple submitters, no conflicts
1324951	NM_017739.4(POMGNT1):c.1623T>G (p.Tyr541Ter)	POMGNT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1355167	NM_017739.4(POMGNT1):c.1365del (p.Arg455fs)	POMGNT1	Pathogenic	criteria provided, single submitter
1372541	NM_017739.4(POMGNT1):c.1153G>T (p.Glu385Ter)	POMGNT1	Pathogenic	criteria provided, single submitter
1399654	NM_017739.4(POMGNT1):c.263del (p.Pro88fs)	POMGNT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1424394	NM_017739.4(POMGNT1):c.75del (p.Thr24_Trp25insTer)	POMGNT1	Pathogenic	criteria provided, single submitter
1450461	NM_017739.4(POMGNT1):c.617G>A (p.Trp206Ter)	POMGNT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1451968	NM_017739.4(POMGNT1):c.563_564del (p.Thr188fs)	POMGNT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1452264	NM_017739.4(POMGNT1):c.1788C>A (p.Cys596Ter)	POMGNT1	Pathogenic	criteria provided, single submitter
1453709	NM_017739.4(POMGNT1):c.75G>A (p.Trp25Ter)	POMGNT1	Pathogenic	criteria provided, single submitter
1459033	NC_000001.10:g.(?46654381)(46656466_?)del	POMGNT1	Pathogenic	criteria provided, single submitter
1459036	NC_000001.10:g.(?46663448)(46664153_?)del	POMGNT1	Pathogenic	criteria provided, single submitter
1499469	NM_017739.4(POMGNT1):c.1785+1G>A	POMGNT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1919294	NM_017739.4(POMGNT1):c.1411A>T (p.Lys471Ter)	POMGNT1	Pathogenic	criteria provided, single submitter
1934388	NM_017739.4(POMGNT1):c.603_618delinsTCCCTTCAGATTCCTGA (p.Ala203fs)	POMGNT1	Pathogenic	criteria provided, single submitter
1945000	NM_017739.4(POMGNT1):c.1615_1616del (p.Glu539fs)	POMGNT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1988629	NM_017739.4(POMGNT1):c.390del (p.Ile131fs)	POMGNT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1996060	NM_017739.4(POMGNT1):c.1055_1059del (p.Gly352fs)	POMGNT1	Pathogenic	criteria provided, single submitter
2000675	NM_017739.4(POMGNT1):c.20del (p.Ser7fs)	POMGNT1	Pathogenic	criteria provided, single submitter
2008105	NM_017739.4(POMGNT1):c.1672dup (p.Ser558fs)	POMGNT1	Pathogenic	criteria provided, single submitter
2012115	NM_017739.4(POMGNT1):c.389dup (p.Ile131fs)	POMGNT1	Pathogenic	criteria provided, single submitter
2015596	NM_017739.4(POMGNT1):c.1A>G (p.Met1Val)	POMGNT1	Pathogenic	criteria provided, single submitter
2018035	NM_017739.4(POMGNT1):c.586del (p.Leu196fs)	POMGNT1	Pathogenic	criteria provided, single submitter
2025161	NM_017739.4(POMGNT1):c.1465G>T (p.Glu489Ter)	POMGNT1	Pathogenic	criteria provided, single submitter
2072367	NM_017739.4(POMGNT1):c.990_991insAA (p.Gln331fs)	POMGNT1	Pathogenic	criteria provided, single submitter
2081702	NM_017739.4(POMGNT1):c.3G>A (p.Met1Ile)	POMGNT1	Pathogenic	criteria provided, single submitter
2112726	NM_017739.4(POMGNT1):c.1352G>A (p.Trp451Ter)	POMGNT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1066260	NM_017739.4(POMGNT1):c.1110+1G>A	TSPAN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1072341	NM_017739.4(POMGNT1):c.595C>T (p.Gln199Ter)	TSPAN1	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 17 · 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
POMGNT1	Definitive	Autosomal recessive	muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A3	17

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
POMGNT1	Orphanet:206564	POMGNT1-related limb-girdle muscular dystrophy R15
POMGNT1	Orphanet:370959	Congenital muscular dystrophy with cerebellar involvement
POMGNT1	Orphanet:588	Muscle-eye-brain disease
POMGNT1	Orphanet:791	Retinitis pigmentosa
POMGNT1	Orphanet:899	Walker-Warburg syndrome

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
POMGNT1	HGNC:19139	ENSG00000085998	Q8WZA1	Protein O-linked-mannose beta-1,2-N-acetylglucosaminyltransferase 1	gencc,clinvar
TSPAN1	HGNC:20657	ENSG00000117472	O60635	Tetraspanin-1	clinvar
LURAP1	HGNC:32327	ENSG00000171357	Q96LR2	Leucine rich adaptor protein 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
POMGNT1	Protein O-linked-mannose beta-1,2-N-acetylglucosaminyltransferase 1	Participates in O-mannosyl glycosylation by catalyzing the addition of N-acetylglucosamine to O-linked mannose on glycoproteins.
TSPAN1	Tetraspanin-1	Structural component of specialized membrane microdomains known as tetraspanin-enriched microdomains (TERMs), which act as platforms for receptor clustering and signaling.
LURAP1	Leucine rich adaptor protein 1	Acts as an activator of the canonical NF-kappa-B pathway and drive the production of pro-inflammatory cytokines.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.33

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
Enzyme (other)	1	4.0×	0.460
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
POMGNT1	Enzyme (other)	yes	2.4.1.312	Glyco_trans_13, Nucleotide-diphossugar_trans, POMGNT1_PANDER-like
TSPAN1	Other/Unknown	no		Tetraspanin_animals, Tetraspanin_EC2_sf, Tetraspanin/Peripherin
LURAP1	Other/Unknown	no		LURAP1, LURA1/LRA25

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
C1 segment of cervical spinal cord	2
adenohypophysis	1
apex of heart	1
bronchial epithelial cell	1
epithelium of bronchus	1
mucosa of transverse colon	1
descending thoracic aorta	1
spinal cord	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
POMGNT1	269	ubiquitous	marker	apex of heart, C1 segment of cervical spinal cord, adenohypophysis
TSPAN1	206	broad	marker	bronchial epithelial cell, epithelium of bronchus, mucosa of transverse colon
LURAP1	161	ubiquitous	yes	C1 segment of cervical spinal cord, spinal cord, descending thoracic aorta

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
POMGNT1	1,164
TSPAN1	949
LURAP1	578

Structural data

PDB: 1 · AlphaFold-only: 2 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
POMGNT1	Q8WZA1	10

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TSPAN1	O60635	88.31
LURAP1	Q96LR2	60.05

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 3 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
Defective POMGNT1 causes MDDGA3, MDDGB3 and MDDGC3	1	5710.0×	6e-04	POMGNT1
DAG1 core M1 glycosylations	1	2855.0×	6e-04	POMGNT1
DAG1 core M2 glycosylations	1	2284.0×	6e-04	POMGNT1
Matriglycan biosynthesis on DAG1	1	815.7×	0.001	POMGNT1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
localization of cell	1	936.2×	0.008	POMGNT1
reactive gliosis	1	802.5×	0.008	POMGNT1
protein O-linked glycosylation via mannose	1	312.1×	0.014	POMGNT1
dentate gyrus development	1	208.1×	0.015	POMGNT1
basement membrane organization	1	170.2×	0.015	POMGNT1
protein O-linked glycosylation via N-acetylgalactosamine	1	144.0×	0.015	POMGNT1
positive regulation of cytokine production	1	90.6×	0.019	LURAP1
myelination	1	83.8×	0.019	POMGNT1
protein O-linked glycosylation	1	74.9×	0.019	POMGNT1
sensory perception of sound	1	33.6×	0.038	POMGNT1
gene expression	1	26.6×	0.044	POMGNT1
positive regulation of canonical NF-kappaB signal transduction	1	24.2×	0.044	LURAP1
protein stabilization	1	22.3×	0.044	TSPAN1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
POMGNT1	0	0
TSPAN1	0	0
LURAP1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
POMGNT1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
POMGNT1	2.4.1.312	protein O-mannose beta-1,4-N-acetylglucosaminyltransferase

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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	1	POMGNT1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	TSPAN1, LURAP1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
POMGNT1	1	—
TSPAN1	0	—
LURAP1	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