myopathy caused by variation in POMT2

Summary

myopathy caused by variation in POMT2 (MONDO:0700071) is a disease caused by POMT2 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: POMT2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 2

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	myopathy caused by variation in POMT2
Mondo ID	MONDO:0700071
GARD	0026344
Is cancer (heuristic)	no

Also known as: myopathy caused by mutation in POMT2 · POMT2 myopathy · POMT2-related myopathy

Data availability: 2 ClinVar variants · 1 GenCC gene-disease record.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › muscle tissue disorder › skeletal muscle disorder › myopathy › myopathy caused by variation in POMT2

Related subtypes (31): polyglucosan body myopathy, muscular atrophy, myopathy of extraocular muscle, acute quadriplegic myopathy, myofascial pain syndrome, myopathy with abnormal lipid metabolism, proximal myopathy with focal depletion of mitochondria, Brody myopathy, rippling muscle disease, myopathy due to myoadenylate deaminase deficiency, proximal myopathy with extrapyramidal signs, intermediate nemaline myopathy, hereditary inclusion-body myopathy, hereditary continuous muscle fiber activity, congenital myopathy, muscular dystrophy, metabolic myopathy, myositis disease, collagen 6-related myopathy, myopathy caused by variation in CRPPA, drug-induced myopathy, myopathy caused by variation in FKRP, myopathy caused by variation in FKTN, myopathy caused by variation in POMGNT1, myopathy caused by variation in POMGNT2, myopathy caused by variation in POMT1, myopathy caused by variation in GMPPB, FHL1-related myopathy, myopathy, sarcoplasmic body, myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis 2, myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis

Subtypes (3): muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2, muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B2, autosomal recessive limb-girdle muscular dystrophy type 2N

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

2 retrieved; paginated sample, class counts are floors:

2 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
1377850	NM_013382.7(POMT2):c.1117-12C>G	POMT2	Uncertain significance	criteria provided, multiple submitters, no conflicts
284056	NM_013382.7(POMT2):c.1711C>T (p.Pro571Ser)	POMT2	Uncertain significance	criteria provided, multiple submitters, no conflicts

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	Strong	Autosomal recessive	myopathy caused by variation in POMT2	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.