muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B2

Summary

muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B2 (MONDO:0013160) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 983

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B2
Mondo ID	MONDO:0013160
OMIM	613156
DOID	DOID:0112380
NCIT	C126690
UMLS	C3150416
MedGen	461766
GARD	0024905
Is cancer (heuristic)	no

Also known as: congenital muscular dystrophy-dystroglycanopathy with intellectual disability type B2 · congenital muscular dystrophy-dystroglycanopathy with mental retardation type B2 · congenital muscular dystrophy-POMT2 related · MDDGB2 · muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B, 2 · muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 2

Data availability: 983 ClinVar variants · 1 GenCC gene-disease record.

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 B › muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B2

Related subtypes (7): muscular dystrophy-dystroglycanopathy type B5, muscular dystrophy-dystroglycanopathy type B6, muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B3, muscular dystrophy-dystroglycanopathy (congenital without intellectual disability), type B4, muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1, muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B14, muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 15

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:

302 likely benign, 175 uncertain significance, 46 conflicting classifications of pathogenicity, 31 pathogenic, 18 likely pathogenic, 12 benign, 11 pathogenic/likely pathogenic, 5 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1430797	NM_013382.7(POMT2):c.678G>A (p.Trp226Ter)	LOC130056175	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
211951	NM_013382.7(POMT2):c.678del (p.Trp226fs)	LOC130056175	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1070813	NM_013382.7(POMT2):c.1034_1035del (p.Val345fs)	POMT2	Pathogenic	criteria provided, single submitter
1073316	NM_013382.7(POMT2):c.1237C>T (p.Arg413Ter)	POMT2	Pathogenic	criteria provided, multiple submitters, no conflicts
1074015	NM_013382.7(POMT2):c.1555G>T (p.Glu519Ter)	POMT2	Pathogenic	criteria provided, single submitter
1416054	NM_013382.7(POMT2):c.1300del (p.Arg434fs)	POMT2	Pathogenic	criteria provided, single submitter
1433335	NM_013382.7(POMT2):c.879_880del (p.Thr295fs)	POMT2	Pathogenic	criteria provided, multiple submitters, no conflicts
162597	NM_013382.7(POMT2):c.1261C>T (p.Arg421Trp)	POMT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1969838	NM_013382.7(POMT2):c.1130T>A (p.Leu377Ter)	POMT2	Pathogenic	criteria provided, single submitter
2033046	NM_013382.7(POMT2):c.1981del (p.Leu661fs)	POMT2	Pathogenic	criteria provided, single submitter
2089840	NM_013382.7(POMT2):c.524_533del (p.Leu175fs)	POMT2	Pathogenic	criteria provided, single submitter
2122163	NM_013382.7(POMT2):c.70dup (p.Gln24fs)	POMT2	Pathogenic	criteria provided, single submitter
2202245	NM_013382.7(POMT2):c.127A>T (p.Lys43Ter)	POMT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2420326	NM_013382.7(POMT2):c.1243G>T (p.Glu415Ter)	POMT2	Pathogenic	criteria provided, single submitter
242416	NM_013382.5(POMT2):c.1170_1171del	POMT2	Pathogenic	criteria provided, single submitter
2425862	NC_000014.8:g.(?77755085)(77762636_?)del	POMT2	Pathogenic	criteria provided, single submitter
2429238	NM_013382.7(POMT2):c.786G>A (p.Trp262Ter)	POMT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2431196	NM_013382.7(POMT2):c.437del (p.Gly146fs)	POMT2	Pathogenic	criteria provided, single submitter
2432830	NM_013382.7(POMT2):c.333+1G>A	POMT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2500946	NM_013382.7(POMT2):c.333+1G>T	POMT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2678033	NM_013382.7(POMT2):c.287A>G (p.Tyr96Cys)	POMT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
282447	NM_013382.7(POMT2):c.1123_1124dup (p.Tyr376fs)	POMT2	Pathogenic	criteria provided, multiple submitters, no conflicts
285471	NM_013382.7(POMT2):c.1658dup (p.Asn553fs)	POMT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
289683	NM_013382.7(POMT2):c.958C>T (p.Gln320Ter)	POMT2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
289765	NM_013382.7(POMT2):c.924-2A>G	POMT2	Pathogenic	criteria provided, multiple submitters, no conflicts
2921970	NM_013382.7(POMT2):c.2147+1G>A	POMT2	Pathogenic	criteria provided, single submitter
2922185	NM_013382.7(POMT2):c.118_119del (p.Arg40fs)	POMT2	Pathogenic	criteria provided, single submitter
2923402	NM_013382.7(POMT2):c.1768dup (p.Tyr590fs)	POMT2	Pathogenic	criteria provided, single submitter
2923579	NM_013382.7(POMT2):c.1927_1943del (p.Val643fs)	POMT2	Pathogenic	criteria provided, single submitter
2923998	NM_013382.7(POMT2):c.1661del (p.Ser554fs)	POMT2	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
POMT2	Definitive	Autosomal recessive	muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
POMT2	Orphanet:206559	POMT2-related limb-girdle muscular dystrophy R14
POMT2	Orphanet:370959	Congenital muscular dystrophy with cerebellar involvement
POMT2	Orphanet:370968	Congenital muscular dystrophy with intellectual disability
POMT2	Orphanet:588	Muscle-eye-brain disease
POMT2	Orphanet:899	Walker-Warburg 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
POMT2	HGNC:19743	ENSG00000009830	Q9UKY4	Protein O-mannosyl-transferase 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
POMT2	Protein O-mannosyl-transferase 2	Transfers mannosyl residues to the hydroxyl group of serine or threonine residues.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
POMT2	Enzyme (other)	yes	2.4.1.109	ArnT-like_N, MIR_motif, PMT-like

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
left testis	1
right testis	1
testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
POMT2	222	ubiquitous	yes	right testis, left testis, testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
POMT2	1,284

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
POMT2	Q9UKY4	87.96

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. 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
Defective POMT2 causes MDDGA2, MDDGB2 and MDDGC2	1	3806.7×	6e-04	POMT2
Defective POMT1 causes MDDGA1, MDDGB1 and MDDGC1	1	3806.7×	6e-04	POMT2
DAG1 core M1 glycosylations	1	2855.0×	6e-04	POMT2
DAG1 core M2 glycosylations	1	2284.0×	6e-04	POMT2
DAG1 core M3 glycosylations	1	1903.3×	6e-04	POMT2
Regulation of CDH1 posttranslational processing and trafficking to plasma membrane	1	335.9×	0.003	POMT2

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
reactive gliosis	1	2407.4×	0.002	POMT2
protein O-linked glycosylation via mannose	1	936.2×	0.002	POMT2
dentate gyrus development	1	624.1×	0.002	POMT2
basement membrane organization	1	510.7×	0.002	POMT2

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
POMT2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
POMT2	2.4.1.109	dolichyl-phosphate-mannose-protein mannosyltransferase

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	1	POMT2
E	Difficult family or no structure, no drug	0

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)
POMT2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.