muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1

Summary

muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1 (MONDO:0013159) is a disease caused by POMT1 (GenCC Strong), with 3 cohort genes.

At a glance

• Causal gene: POMT1 (GenCC Strong)
• Cohort genes: 3
• ClinVar variants: 969

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 B1
Mondo ID	MONDO:0013159
OMIM	613155
DOID	DOID:0050588
UMLS	C5436962
MedGen	1774807
GARD	0024904
Is cancer (heuristic)	no

Also known as: congenital muscular dystrophy-POMT1 related · MDDGB1 · muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B, 1 · muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 1

Data availability: 969 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 B1

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 B2, 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:

299 likely benign, 165 uncertain significance, 42 conflicting classifications of pathogenicity, 34 pathogenic, 18 benign, 17 pathogenic/likely pathogenic, 14 benign/likely benign, 11 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1066221	NM_001077365.2(POMT1):c.1176-2A>G	POMT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1067618	NM_001077365.2(POMT1):c.427+1G>A	POMT1	Pathogenic	criteria provided, single submitter
1075349	NM_001077365.2(POMT1):c.1204dup (p.His402fs)	POMT1	Pathogenic	criteria provided, single submitter
1076965	NM_001077365.2(POMT1):c.160_161insTTTTTTTTTTTTTTTNNNNNNNNNNTCACCGTTTTAGCCGGGATGGTCTCGATCTCCTGACCTCGTGATCCGCCCGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCGCGCCCGGCCAGTACATCTCTTTTT (p.Tyr54delinsPhePhePhePhePheXaaXaaXaaXaaHisArgPheSerArgAspGlyLeuAspLeuLeuThrSerTer)	POMT1	Pathogenic	criteria provided, single submitter
1192212	NM_001077365.2(POMT1):c.1272+1G>A	POMT1	Pathogenic	criteria provided, multiple submitters, no conflicts
1323489	NM_001077365.2(POMT1):c.633C>G (p.Tyr211Ter)	POMT1	Pathogenic	criteria provided, multiple submitters, no conflicts
1343631	NM_001077365.2(POMT1):c.2040_2050del (p.Val681fs)	POMT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1359283	NM_001077365.2(POMT1):c.859_871del (p.Gly287fs)	POMT1	Pathogenic	criteria provided, single submitter
1360015	NM_001077365.2(POMT1):c.270_280delAATTGGAGCAG (p.Gly92fs)	POMT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1364191	NM_001077365.2(POMT1):c.58dup (p.Val20fs)	POMT1	Pathogenic	criteria provided, single submitter
1399708	NM_001077365.2(POMT1):c.97C>T (p.Arg33Ter)	POMT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1451349	NM_001077365.2(POMT1):c.72del (p.Met25fs)	POMT1	Pathogenic	criteria provided, single submitter
1453137	NM_001077365.2(POMT1):c.1364del (p.Lys455fs)	POMT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1458255	NM_001077365.2(POMT1):c.130G>A (p.Glu44Lys)	POMT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1470886	NM_001077365.2(POMT1):c.605+1G>T	POMT1	Pathogenic	criteria provided, single submitter
1497287	NM_001077365.2(POMT1):c.313C>T (p.Arg105Cys)	POMT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1516923	NC_000009.11:g.(?134389752)(134390863_?)del	POMT1	Pathogenic	criteria provided, single submitter
162594	NM_001077365.2(POMT1):c.1478dup (p.Tyr493Ter)	POMT1	Pathogenic	criteria provided, multiple submitters, no conflicts
1686087	NM_001077365.2(POMT1):c.986+1G>A	POMT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1930280	NM_001077365.2(POMT1):c.720del (p.Leu240fs)	POMT1	Pathogenic	criteria provided, single submitter
194757	NM_001077365.2(POMT1):c.1657del (p.Leu553fs)	POMT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
194859	NM_001077365.2(POMT1):c.1798C>T (p.Arg600Ter)	POMT1	Pathogenic	criteria provided, multiple submitters, no conflicts
1997263	NM_001077365.2(POMT1):c.1061G>A (p.Trp354Ter)	POMT1	Pathogenic	criteria provided, single submitter
1998900	NM_001077365.2(POMT1):c.529C>T (p.Gln177Ter)	POMT1	Pathogenic	criteria provided, single submitter
1998907	NM_001077365.2(POMT1):c.2141G>A (p.Trp714Ter)	POMT1	Pathogenic	criteria provided, single submitter
2020409	NM_001077365.2(POMT1):c.145del (p.Gln49fs)	POMT1	Pathogenic	criteria provided, single submitter
2041522	NM_001077365.2(POMT1):c.789_790del (p.Leu263fs)	POMT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2062446	NM_001077365.2(POMT1):c.2113_2119del (p.Ser705fs)	POMT1	Pathogenic	criteria provided, single submitter
212739	NM_001077365.2(POMT1):c.558G>A (p.Trp186Ter)	POMT1	Pathogenic	criteria provided, single submitter
2181474	NM_001077365.2(POMT1):c.1284_1285del (p.Asn428fs)	POMT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 12 · Orphanet: 7 · 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
POMT1	Definitive	Autosomal recessive	muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1	12

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
POMT1	Orphanet:370959	Congenital muscular dystrophy with cerebellar involvement
POMT1	Orphanet:370968	Congenital muscular dystrophy with intellectual disability
POMT1	Orphanet:370980	Congenital muscular dystrophy without intellectual disability
POMT1	Orphanet:588	Muscle-eye-brain disease
POMT1	Orphanet:86812	POMT1-related limb-girdle muscular dystrophy R11
POMT1	Orphanet:899	Walker-Warburg syndrome
INPP5K	Orphanet:662184	Congenital muscular dystrophy-cataract-intellectual disability 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
POMT1	HGNC:9202	ENSG00000130714	Q9Y6A1	Protein O-mannosyl-transferase 1	gencc,clinvar
PLPP7	HGNC:28174	ENSG00000160539	Q8NBV4	Inactive phospholipid phosphatase 7	clinvar
INPP5K	HGNC:33882	ENSG00000132376	Q9BT40	Inositol polyphosphate 5-phosphatase K	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
POMT1	Protein O-mannosyl-transferase 1	Transfers mannosyl residues to the hydroxyl group of serine or threonine residues.
PLPP7	Inactive phospholipid phosphatase 7	Plays a role as negative regulator of myoblast differentiation, in part through effects on MTOR signaling.
INPP5K	Inositol polyphosphate 5-phosphatase K	Inositol 5-phosphatase which acts on inositol 1,4,5-trisphosphate, inositol 1,3,4,5-tetrakisphosphate, phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate.

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.67

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)	2	8.0×	0.039
Other/Unknown	1	0.6×	0.914

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
POMT1	Enzyme (other)	yes	2.4.1.109	ArnT-like_N, MIR_motif, PMT-like
PLPP7	Other/Unknown	no		PAP2/HPO, PAP2/HPO_sf
INPP5K	Enzyme (other)	yes	3.1.3.56	IPPc, Endo/exonu/phosph_ase_sf, SKICH

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
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1
apex of heart	1
gastrocnemius	1
hindlimb stylopod muscle	1
pigmented layer of retina	1
right lobe of thyroid gland	1
right lung	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
POMT1	264	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
PLPP7	195	ubiquitous	yes	apex of heart, hindlimb stylopod muscle, gastrocnemius
INPP5K	283	ubiquitous	marker	pigmented layer of retina, right lung, right lobe of thyroid gland

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
POMT1	1,475
INPP5K	1,300
PLPP7	481

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
INPP5K	Q9BT40	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
POMT1	Q9Y6A1	88.09
PLPP7	Q8NBV4	80.10

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 11. Enrichment computed across 3 evidence-associated genes (2 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 2 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	1903.3×	0.002	POMT1
Defective POMT1 causes MDDGA1, MDDGB1 and MDDGC1	1	1903.3×	0.002	POMT1
DAG1 core M1 glycosylations	1	1427.5×	0.002	POMT1
DAG1 core M2 glycosylations	1	1142.0×	0.002	POMT1
DAG1 core M3 glycosylations	1	951.7×	0.002	POMT1
PI Metabolism	1	178.4×	0.009	INPP5K
Regulation of CDH1 posttranslational processing and trafficking to plasma membrane	1	167.9×	0.009	POMT1
Synthesis of PIPs at the plasma membrane	1	105.7×	0.012	INPP5K
Phospholipid metabolism	1	100.2×	0.012	INPP5K
Metabolism of lipids	1	15.8×	0.069	INPP5K
Metabolism	1	5.8×	0.165	INPP5K

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
positive regulation of renal water transport	1	5617.3×	0.006	INPP5K
negative regulation of dephosphorylation	1	1404.3×	0.007	INPP5K
negative regulation of D-glucose transmembrane transport	1	1123.5×	0.007	INPP5K
negative regulation of protein targeting to membrane	1	936.2×	0.007	INPP5K
negative regulation of glycogen biosynthetic process	1	702.2×	0.007	INPP5K
regulation of glycogen biosynthetic process	1	624.1×	0.007	INPP5K
negative regulation of calcium ion transport	1	561.7×	0.007	INPP5K
negative regulation of single stranded viral RNA replication via double stranded DNA intermediate	1	510.7×	0.007	INPP5K
positive regulation of urine volume	1	432.1×	0.007	INPP5K
host-mediated suppression of viral transcription	1	432.1×	0.007	INPP5K
ruffle assembly	1	432.1×	0.007	INPP5K
negative regulation of myotube differentiation	1	374.5×	0.007	PLPP7
protein O-linked glycosylation via mannose	1	312.1×	0.008	POMT1
phosphatidylinositol dephosphorylation	1	216.1×	0.011	INPP5K
negative regulation of stress fiber assembly	1	193.7×	0.011	INPP5K
cellular response to hormone stimulus	1	127.7×	0.015	INPP5K
negative regulation of insulin receptor signaling pathway	1	124.8×	0.015	INPP5K
phosphatidylinositol biosynthetic process	1	122.1×	0.015	INPP5K
cellular response to epidermal growth factor stimulus	1	106.0×	0.016	INPP5K
cellular response to cAMP	1	96.8×	0.016	INPP5K
negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	87.8×	0.017	INPP5K
protein O-linked glycosylation	1	74.9×	0.019	POMT1
cellular response to insulin stimulus	1	56.7×	0.024	INPP5K
cellular response to tumor necrosis factor	1	54.5×	0.024	INPP5K
glucose homeostasis	1	43.5×	0.029	INPP5K
extracellular matrix organization	1	40.7×	0.030	POMT1
protein localization to plasma membrane	1	36.2×	0.032	INPP5K
actin cytoskeleton organization	1	26.4×	0.043	INPP5K
in utero embryonic development	1	24.0×	0.045	INPP5K
G protein-coupled receptor signaling pathway	1	12.1×	0.086	INPP5K

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 3 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
POMT1	0	0
PLPP7	0	0
INPP5K	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
POMT1	2.4.1.109	dolichyl-phosphate-mannose-protein mannosyltransferase
INPP5K	3.1.3.56	inositol-polyphosphate 5-phosphatase

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	INPP5K
D	Druggable family + AlphaFold only, no drug	1	POMT1
E	Difficult family or no structure, no drug	1	PLPP7

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)
POMT1	0	—
PLPP7	0	—
INPP5K	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.