muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A3

disease

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Also known as MDDGA3muscle-eye-brain-POMGNT1 relatedmuscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies) type A, 3muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 3

Summary

muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A3 (MONDO:0009667) is a disease caused by POMGNT1 (GenCC Definitive), with 2 cohort genes.

At a glance

Causal gene: POMGNT1 (GenCC Definitive)
Cohort genes: 2
ClinVar variants: 213

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A3
Mondo ID	MONDO:0009667
OMIM	253280
DOID	DOID:0111236
NCIT	C126740
UMLS	C3151519
MedGen	462869
GARD	0015204
Is cancer (heuristic)	no

Also known as: MDDGA3 · muscle-eye-brain-POMGNT1 related · muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies) type A, 3 · muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 3

Data availability: 213 ClinVar variants · 4 GenCC gene-disease records · 1 cell line.

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 A › muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A3

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

213 retrieved; paginated sample, class counts are floors:

86 likely pathogenic, 40 uncertain significance, 36 pathogenic/likely pathogenic, 23 conflicting classifications of pathogenicity, 18 pathogenic, 9 benign, 1 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1499469	NM_017739.4(POMGNT1):c.1785+1G>A	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
2112726	NM_017739.4(POMGNT1):c.1352G>A (p.Trp451Ter)	POMGNT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
265399	NM_017739.4(POMGNT1):c.636C>T (p.Phe212=)	POMGNT1	Pathogenic	criteria provided, multiple submitters, no conflicts
2939228	NM_017739.4(POMGNT1):c.1835G>A (p.Trp612Ter)	POMGNT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
370969	NM_017739.4(POMGNT1):c.1694_1695del (p.Ser565fs)	POMGNT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
371286	NM_017739.4(POMGNT1):c.185_186insA (p.Arg63fs)	POMGNT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
371543	NM_017739.4(POMGNT1):c.478del (p.Met160fs)	POMGNT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3989	NM_017739.4(POMGNT1):c.1719del (p.His573fs)	POMGNT1	Pathogenic/Likely pathogenic	no assertion criteria provided
3990	NM_017739.4(POMGNT1):c.1478C>G (p.Pro493Arg)	POMGNT1	Pathogenic	no assertion criteria provided
3993	NM_017739.4(POMGNT1):c.932G>A (p.Arg311Gln)	POMGNT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3994	NM_017739.4(POMGNT1):c.187C>T (p.Arg63Ter)	POMGNT1	Pathogenic	criteria provided, multiple submitters, no conflicts
3995	NM_017739.4(POMGNT1):c.1832del (p.Leu611fs)	POMGNT1	Pathogenic	no assertion criteria provided
3996	NM_017739.4(POMGNT1):c.1425G>A (p.Trp475Ter)	POMGNT1	Pathogenic	criteria provided, single submitter
3999	NM_017739.4(POMGNT1):c.652+1G>A	POMGNT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4000	NM_017739.4(POMGNT1):c.1469G>A (p.Cys490Tyr)	POMGNT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
551169	NM_017739.4(POMGNT1):c.458C>G (p.Ser153Ter)	POMGNT1	Pathogenic	criteria provided, multiple submitters, no conflicts
557018	NM_017739.4(POMGNT1):c.1895+1G>C	POMGNT1	Pathogenic	criteria provided, single submitter
558512	NM_017739.4(POMGNT1):c.385C>T (p.Arg129Trp)	POMGNT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
56578	NM_017739.4(POMGNT1):c.1285-2A>G	POMGNT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
56581	NM_017739.4(POMGNT1):c.1350_1354del (p.Trp451fs)	POMGNT1	Pathogenic	criteria provided, multiple submitters, no conflicts
56582	NM_017739.4(POMGNT1):c.1539+1G>A	POMGNT1	Pathogenic	criteria provided, multiple submitters, no conflicts
56591	NM_017739.4(POMGNT1):c.1876del (p.Val626fs)	POMGNT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
56593	NM_017739.4(POMGNT1):c.1895+1G>T	POMGNT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
56610	NM_017739.4(POMGNT1):c.931C>T (p.Arg311Ter)	POMGNT1	Pathogenic	criteria provided, multiple submitters, no conflicts
648374	NM_017739.4(POMGNT1):c.511C>T (p.Arg171Ter)	POMGNT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
665448	NM_017739.4(POMGNT1):c.1462C>T (p.Arg488Ter)	POMGNT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
872288	NM_017739.4(POMGNT1):c.1325G>A (p.Arg442His)	POMGNT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
984973	NM_017739.4(POMGNT1):c.304G>T (p.Glu102Ter)	POMGNT1	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

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

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

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

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.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.5

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	6.0×	0.320
Other/Unknown	1	0.9×	0.805

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

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)	2
unknown	0

Top tissues across cohort

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

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
POMGNT1	1,164
TSPAN1	949

Structural data

PDB: 1 · AlphaFold-only: 1 · 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

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 2 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 2 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	1404.3×	0.005	POMGNT1
reactive gliosis	1	1203.7×	0.005	POMGNT1
protein O-linked glycosylation via mannose	1	468.1×	0.008	POMGNT1
dentate gyrus development	1	312.1×	0.008	POMGNT1
basement membrane organization	1	255.3×	0.008	POMGNT1
protein O-linked glycosylation via N-acetylgalactosamine	1	216.1×	0.008	POMGNT1
myelination	1	125.8×	0.012	POMGNT1
protein O-linked glycosylation	1	112.3×	0.012	POMGNT1
sensory perception of sound	1	50.5×	0.024	POMGNT1
gene expression	1	39.9×	0.027	POMGNT1
protein stabilization	1	33.4×	0.030	TSPAN1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 1 of 2 evidence-associated genes (50%) 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

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: 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	1	POMGNT1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	TSPAN1

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)
POMGNT1	1	—
TSPAN1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: POMGNT1, TSPAN1