Muscle-eye-brain disease

disease

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Also known as MEBMEB syndromemuscle eye brain diseasemuscle-eye-brain syndromemuscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A3Santavuori congenital muscular dystrophy

Summary

Muscle-eye-brain disease (MONDO:0018939) is a disease (an umbrella term covering 9 Mondo subtypes) caused by variants in POMGNT1 and RXYLT1, with 9 cohort genes and 1 clinical trial. The dominant Reactome pathway is Matriglycan biosynthesis on DAG1 (4 cohort genes).

At a glance

Prevalence: Unknown (Worldwide)
Causal genes: POMGNT1 (GenCC Definitive), RXYLT1 (GenCC Definitive)
Umbrella term: 9 Mondo subtypes
Cohort genes: 9
ClinVar variants: 255
Phenotypes (HPO): 23
Clinical trials: 1

Clinical features

Signs & symptoms

Clinical features (HPO)

23 HPO clinical features (Orphanet curated; top 23 by frequency):

HPO ID	Term	Frequency
HP:0000238	Hydrocephalus	Very frequent (80-99%)
HP:0000486	Strabismus	Very frequent (80-99%)
HP:0000501	Glaucoma	Very frequent (80-99%)
HP:0000505	Visual impairment	Very frequent (80-99%)
HP:0000545	Myopia	Very frequent (80-99%)
HP:0000648	Optic atrophy	Very frequent (80-99%)
HP:0001288	Gait disturbance	Very frequent (80-99%)
HP:0002167	Abnormality of speech or vocalization	Very frequent (80-99%)
HP:0002353	EEG abnormality	Very frequent (80-99%)
HP:0003198	Myopathy	Very frequent (80-99%)
HP:0003236	Elevated circulating creatine kinase concentration	Very frequent (80-99%)
HP:0003457	EMG abnormality	Very frequent (80-99%)
HP:0100543	Cognitive impairment	Very frequent (80-99%)
HP:0000518	Cataract	Frequent (30-79%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0001252	Hypotonia	Frequent (30-79%)
HP:0001276	Hypertonia	Frequent (30-79%)
HP:0001608	Abnormality of the voice	Frequent (30-79%)
HP:0100022	Abnormality of movement	Frequent (30-79%)
HP:0001360	Holoprosencephaly	Occasional (5-29%)
HP:0002435	Meningocele	Occasional (5-29%)
HP:0004374	Hemiplegia/hemiparesis	Occasional (5-29%)
HP:0007360	Aplasia/Hypoplasia of the cerebellum	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	muscle-eye-brain disease
Mondo ID	MONDO:0018939
Orphanet	588
SNOMED CT	277950001
UMLS	C0457133
MedGen	105341
GARD	0000156
Is cancer (heuristic)	no

Also known as: MEB · MEB syndrome · muscle eye brain disease · muscle-eye-brain syndrome · muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A3 · Santavuori congenital muscular dystrophy

Data availability: 255 ClinVar variants · 9 GenCC gene-disease records.

Disease family

An umbrella term covering 9 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › congenital muscular dystrophy › muscle-eye-brain disease

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

255 retrieved; paginated sample, class counts are floors:

119 uncertain significance, 37 conflicting classifications of pathogenicity, 31 likely pathogenic, 27 pathogenic/likely pathogenic, 22 likely benign, 14 pathogenic, 3 benign/likely benign, 2 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1451968	NM_017739.4(POMGNT1):c.563_564del (p.Thr188fs)	POMGNT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1945000	NM_017739.4(POMGNT1):c.1615_1616del (p.Glu539fs)	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
2948415	NM_017739.4(POMGNT1):c.727_728del (p.Asp243fs)	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
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
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
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
56598	NM_017739.4(POMGNT1):c.351del (p.Thr118fs)	POMGNT1	Pathogenic	criteria provided, multiple submitters, no conflicts
56599	NM_017739.4(POMGNT1):c.447del (p.Phe149fs)	POMGNT1	Pathogenic	criteria provided, single submitter
56601	NM_017739.4(POMGNT1):c.593del (p.Ser198fs)	POMGNT1	Pathogenic	criteria provided, single submitter
56603	NM_017739.4(POMGNT1):c.630G>T (p.Trp210Cys)	POMGNT1	Pathogenic/Likely pathogenic	no assertion criteria provided
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
1323487	NM_017739.4(POMGNT1):c.878del (p.Pro293fs)	TSPAN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1525403	NM_017739.4(POMGNT1):c.880-1G>C	TSPAN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2158255	NM_017739.4(POMGNT1):c.1609A>T (p.Lys537Ter)	TSPAN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2677987	NM_017739.4(POMGNT1):c.1287dup	TSPAN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3748753	NM_017739.4(POMGNT1):c.1249dup (p.Asp417fs)	TSPAN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3988	NM_017739.4(POMGNT1):c.1649G>A (p.Ser550Asn)	TSPAN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 94 · Orphanet: 37 · 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
B3GALNT2	Definitive	Autosomal recessive	muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 11	10
FKRP	Definitive	Autosomal recessive	muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A5	15
FKTN	Definitive	Autosomal recessive	muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4	13
GMPPB	Definitive	Autosomal recessive	muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A14	12
POMGNT1	Definitive	Autosomal recessive	muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A3	17
POMT1	Definitive	Autosomal recessive	muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1	12
POMT2	Definitive	Autosomal recessive	muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2	10
RXYLT1	Definitive	Autosomal recessive	muscle-eye-brain disease	5

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
RXYLT1	Orphanet:899	Walker-Warburg syndrome
FKRP	Orphanet:34515	FKRP-related limb-girdle muscular dystrophy R9
FKRP	Orphanet:370959	Congenital muscular dystrophy with cerebellar involvement
FKRP	Orphanet:370968	Congenital muscular dystrophy with intellectual disability
FKRP	Orphanet:370980	Congenital muscular dystrophy without intellectual disability
FKRP	Orphanet:588	Muscle-eye-brain disease
FKRP	Orphanet:899	Walker-Warburg syndrome
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
GMPPB	Orphanet:353327	Congenital myasthenic syndrome with glycosylation defect
GMPPB	Orphanet:363623	GMPPB-related limb-girdle muscular dystrophy R19
GMPPB	Orphanet:370959	Congenital muscular dystrophy with cerebellar involvement
GMPPB	Orphanet:370968	Congenital muscular dystrophy with intellectual disability
GMPPB	Orphanet:588	Muscle-eye-brain disease
B3GALNT2	Orphanet:588	Muscle-eye-brain disease
B3GALNT2	Orphanet:88616	Autosomal recessive non-syndromic intellectual disability
B3GALNT2	Orphanet:899	Walker-Warburg syndrome
FKTN	Orphanet:154	Familial isolated dilated cardiomyopathy
FKTN	Orphanet:206554	Fukutin-related limb-girdle muscular dystrophy R13
FKTN	Orphanet:272	Congenital muscular dystrophy, Fukuyama type
FKTN	Orphanet:370980	Congenital muscular dystrophy without intellectual disability
FKTN	Orphanet:588	Muscle-eye-brain disease
FKTN	Orphanet:899	Walker-Warburg syndrome
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

Cohort genes → proteins

9 cohort genes, 9 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	9

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
RXYLT1	HGNC:13530	ENSG00000118600	Q9Y2B1	Ribitol-5-phosphate xylosyltransferase 1	gencc
FKRP	HGNC:17997	ENSG00000181027	Q9H9S5	Ribitol 5-phosphate transferase FKRP	gencc
POMT2	HGNC:19743	ENSG00000009830	Q9UKY4	Protein O-mannosyl-transferase 2	gencc
GMPPB	HGNC:22932	ENSG00000173540	Q9Y5P6	Mannose-1-phosphate guanylyltransferase catalytic subunit beta	gencc
B3GALNT2	HGNC:28596	ENSG00000162885	Q8NCR0	UDP-GalNAc:beta-1,3-N-acetylgalactosaminyltransferase 2	gencc
FKTN	HGNC:3622	ENSG00000106692	O75072	Ribitol-5-phosphate transferase FKTN	gencc
POMT1	HGNC:9202	ENSG00000130714	Q9Y6A1	Protein O-mannosyl-transferase 1	gencc
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.
RXYLT1	Ribitol-5-phosphate xylosyltransferase 1	Acts as a UDP-D-xylose:ribitol-5-phosphate beta1,4-xylosyltransferase, which catalyzes the transfer of UDP-D-xylose to ribitol 5-phosphate (Rbo5P) to form the Xylbeta1-4Rbo5P linkage on O-mannosyl glycan.
FKRP	Ribitol 5-phosphate transferase FKRP	Catalyzes the transfer of a ribitol 5-phosphate from CDP-L-ribitol to the ribitol 5-phosphate previously attached by FKTN/fukutin to the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-beta-3-N-acetylglucosamine-beta-4-(phos…
POMT2	Protein O-mannosyl-transferase 2	Transfers mannosyl residues to the hydroxyl group of serine or threonine residues.
GMPPB	Mannose-1-phosphate guanylyltransferase catalytic subunit beta	Catalytic subunit of the GMPPA-GMPPB mannose-1-phosphate guanylyltransferase complex.
B3GALNT2	UDP-GalNAc:beta-1,3-N-acetylgalactosaminyltransferase 2	Beta-1,3-N-acetylgalactosaminyltransferase that synthesizes a unique carbohydrate structure, GalNAc-beta-1-3GlcNAc, on N- and O-glycans.
FKTN	Ribitol-5-phosphate transferase FKTN	Catalyzes the transfer of a ribitol-phosphate from CDP-ribitol to the distal N-acetylgalactosamine of the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-beta-3-N-acetylglucosamine-beta-4-(phosphate-6-)mannose), a carbohydra…
POMT1	Protein O-mannosyl-transferase 1	Transfers mannosyl residues to the hydroxyl group of serine or threonine residues.
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: 6 · Difficult: 0 · Unknown: 3 · 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)	6	8.0×	4e-05
Other/Unknown	3	0.6×	0.955

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
RXYLT1	Enzyme (other)	yes	2.4.2.61	RXYLT1-like, RXYLT1_C, RXYLT1_N
FKRP	Other/Unknown	no		LicD/FKTN/FKRP_NTP_transf, LicD_transferase, FKRP_N
POMT2	Enzyme (other)	yes	2.4.1.109	ArnT-like_N, MIR_motif, PMT-like
GMPPB	Enzyme (other)	yes	2.7.7.13	NTP_transferase_dom, Hexapep_transf_CS, Nucleotide-diphossugar_trans
B3GALNT2	Enzyme (other)	yes	2.4.1.313	Glyco_trans_31
FKTN	Other/Unknown	no		LicD/FKTN/FKRP_NTP_transf, FKTN/MNN-like, FKTN_N
POMT1	Enzyme (other)	yes	2.4.1.109	ArnT-like_N, MIR_motif, PMT-like
TSPAN1	Other/Unknown	no		Tetraspanin_animals, Tetraspanin_EC2_sf, Tetraspanin/Peripherin

Expression context

Cohort genes with no expression data: 0.

7 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)	9
unknown	0

Top tissues across cohort

Tissue	Cohort genes
adenohypophysis	2
body of pancreas	2
mucosa of transverse colon	2
adrenal tissue	2
C1 segment of cervical spinal cord	1
apex of heart	1
caput epididymis	1
corpus epididymis	1
cranial nerve II	1
cardiac muscle of right atrium	1
hindlimb stylopod muscle	1
left ventricle myocardium	1
left testis	1
right testis	1
testis	1
skeletal muscle tissue	1
calcaneal tendon	1
germinal epithelium of ovary	1
cerebellar cortex	1
cerebellar hemisphere	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
RXYLT1	293	ubiquitous	marker	corpus epididymis, caput epididymis, cranial nerve II
FKRP	230	ubiquitous	marker	left ventricle myocardium, cardiac muscle of right atrium, hindlimb stylopod muscle
POMT2	222	ubiquitous	yes	right testis, left testis, testis
GMPPB	172	ubiquitous	marker	body of pancreas, adenohypophysis, mucosa of transverse colon
B3GALNT2	141	ubiquitous	marker	body of pancreas, skeletal muscle tissue, adrenal tissue
FKTN	277	ubiquitous	yes	calcaneal tendon, adrenal tissue, germinal epithelium of ovary
POMT1	264	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
TSPAN1	206	broad	marker	bronchial epithelial cell, epithelium of bronchus, mucosa of transverse colon

Protein interactions among cohort

Intra-cohort edges: 28.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GMPPB	2,559
POMT1	1,475
FKRP	1,436
POMT2	1,284
FKTN	1,226
POMGNT1	1,164
TSPAN1	949
B3GALNT2	748
RXYLT1	675

Intra-cohort edges

A	B	Sources
B3GALNT2	FKRP	string_interaction
B3GALNT2	FKTN	string_interaction
B3GALNT2	GMPPB	string_interaction
B3GALNT2	POMGNT1	string_interaction
B3GALNT2	POMT1	string_interaction
B3GALNT2	POMT2	string_interaction
B3GALNT2	RXYLT1	string_interaction
FKRP	FKTN	intact, string_interaction
FKRP	GMPPB	string_interaction
FKRP	POMGNT1	string_interaction
FKRP	POMT1	string_interaction
FKRP	POMT2	string_interaction
FKRP	RXYLT1	intact, string_interaction
FKTN	GMPPB	string_interaction
FKTN	POMGNT1	intact, string_interaction
FKTN	POMT1	string_interaction
FKTN	POMT2	string_interaction
FKTN	RXYLT1	biogrid_interaction, intact, string_interaction
GMPPB	POMGNT1	string_interaction
GMPPB	POMT1	string_interaction
GMPPB	POMT2	string_interaction
GMPPB	RXYLT1	string_interaction
POMGNT1	POMT1	string_interaction
POMGNT1	POMT2	string_interaction
POMGNT1	RXYLT1	biogrid_interaction, intact, string_interaction
POMT1	POMT2	intact, string_interaction
POMT1	RXYLT1	string_interaction
POMT2	RXYLT1	string_interaction

Structural data

PDB: 3 · AlphaFold-only: 6 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
POMGNT1	Q8WZA1	10
FKRP	Q9H9S5	8
GMPPB	Q9Y5P6	3

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FKTN	O75072	92.48
TSPAN1	O60635	88.31
POMT1	Q9Y6A1	88.09
POMT2	Q9UKY4	87.96
B3GALNT2	Q8NCR0	86.81
RXYLT1	Q9Y2B1	85.72

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 12. Enrichment computed across 9 evidence-associated genes (8 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 8 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Matriglycan biosynthesis on DAG1	4	407.9×	1e-09	POMGNT1, RXYLT1, FKRP, FKTN
DAG1 core M1 glycosylations	3	1070.6×	5e-09	POMGNT1, POMT2, POMT1
DAG1 core M2 glycosylations	3	856.5×	9e-09	POMGNT1, POMT2, POMT1
DAG1 core M3 glycosylations	3	713.8×	1e-08	POMT2, B3GALNT2, POMT1
Defective POMT2 causes MDDGA2, MDDGB2 and MDDGC2	2	951.7×	3e-06	POMT2, POMT1
Defective POMT1 causes MDDGA1, MDDGB1 and MDDGC1	2	951.7×	3e-06	POMT2, POMT1
Regulation of CDH1 posttranslational processing and trafficking to plasma membrane	2	84.0×	4e-04	POMT2, POMT1
Defective POMGNT1 causes MDDGA3, MDDGB3 and MDDGC3	1	713.8×	0.002	POMGNT1
Synthesis of GDP-mannose	1	237.9×	0.006	GMPPB
O-linked glycosylation	1	18.1×	0.065	B3GALNT2
Post-translational protein modification	1	2.4×	0.380	B3GALNT2
Metabolism of proteins	1	1.6×	0.491	B3GALNT2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 9 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
protein O-linked glycosylation via mannose	6	624.1×	3e-15	POMGNT1, RXYLT1, FKRP, POMT2, FKTN, POMT1
protein O-linked glycosylation	5	124.8×	5e-09	POMGNT1, RXYLT1, B3GALNT2, FKTN, POMT1
basement membrane organization	4	227.0×	3e-08	POMGNT1, FKRP, POMT2, FKTN
localization of cell	2	624.1×	5e-05	POMGNT1, FKRP
reactive gliosis	2	535.0×	6e-05	POMGNT1, POMT2
skeletal muscle fiber differentiation	2	374.5×	1e-04	FKRP, FKTN
dentate gyrus development	2	138.7×	7e-04	POMGNT1, POMT2
pentitol metabolic process	1	1872.4×	0.003	FKRP
filtration diaphragm assembly	1	1872.4×	0.003	FKRP
pentose metabolic process	1	936.2×	0.006	FKRP
obsolete GDP-mannose biosynthetic process from mannose	1	624.1×	0.008	GMPPB
creatine metabolic process	1	468.1×	0.009	FKRP
connective tissue development	1	468.1×	0.009	FKRP
oxygen metabolic process	1	468.1×	0.009	FKRP
maintenance of protein localization in endoplasmic reticulum	1	374.5×	0.010	FKRP
GDP-mannose biosynthetic process	1	312.1×	0.011	GMPPB
GDP-mannose metabolic process	1	312.1×	0.011	GMPPB
connective tissue replacement	1	267.5×	0.012	FKRP
cerebellar cortex development	1	234.1×	0.013	FKTN
diaphragm development	1	208.1×	0.013	FKRP
protein import	1	187.2×	0.014	FKRP
response to alcohol	1	170.2×	0.015	FKRP
reelin-mediated signaling pathway	1	133.8×	0.018	FKRP
respiratory system process	1	104.0×	0.022	FKRP
glial cell differentiation	1	98.5×	0.022	FKRP
skeletal muscle tissue regeneration	1	98.5×	0.022	FKRP
protein tetramerization	1	69.3×	0.030	FKRP
negative regulation of JNK cascade	1	62.4×	0.032	FKTN
neuromuscular process	1	58.5×	0.033	FKRP
adult walking behavior	1	55.1×	0.034	FKRP

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 9

Druggability breadth: 1 of 9 evidence-associated genes (11%) 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
RXYLT1	0	0
FKRP	0	0
POMT2	0	0
GMPPB	0	0
B3GALNT2	0	0
FKTN	0	0
POMT1	0	0
TSPAN1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 6.

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
RXYLT1	2.4.2.61	alpha-dystroglycan beta1,4-xylosyltransferase
POMT2	2.4.1.109	dolichyl-phosphate-mannose-protein mannosyltransferase
GMPPB	2.7.7.13	mannose-1-phosphate guanylyltransferase
B3GALNT2	2.4.1.313	protein O-mannose beta-1,3-N-acetylgalactosaminyltransferase
POMT1	2.4.1.109	dolichyl-phosphate-mannose-protein mannosyltransferase

Pharmacogenomics

Cohort genes with a PharmGKB record: 9; 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	2	POMGNT1, GMPPB
D	Druggable family + AlphaFold only, no drug	4	RXYLT1, POMT2, B3GALNT2, POMT1
E	Difficult family or no structure, no drug	3	FKRP, FKTN, TSPAN1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
POMGNT1	1	—
RXYLT1	0	—
FKRP	0	—
POMT2	0	—
GMPPB	0	—
B3GALNT2	0	—
FKTN	0	—
POMT1	0	—
TSPAN1	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
NCT04001595	Not specified	UNKNOWN	Global FKRP Registry

Cohort genes: POMGNT1, RXYLT1, FKRP, POMT2, GMPPB, B3GALNT2, FKTN, POMT1, TSPAN1