Muscular dystrophy-dystroglycanopathy

Summary

Muscular dystrophy-dystroglycanopathy (MONDO:0018276) is a disease (an umbrella term covering 7 Mondo subtypes) caused by variants in FKRP and FKTN, with 8 cohort genes. The dominant Reactome pathway is Matriglycan biosynthesis on DAG1 (4 cohort genes).

At a glance

• Causal genes: FKRP (GenCC Strong), FKTN (GenCC Strong)
• Umbrella term: 7 Mondo subtypes
• Cohort genes: 8
• ClinVar variants: 69

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	muscular dystrophy-dystroglycanopathy
Mondo ID	MONDO:0018276
Orphanet	370953
DOID	DOID:0112374
UMLS	C5679911
MedGen	1842215
GARD	0012584
Is cancer (heuristic)	no

Also known as: CMD due to dystroglycanopathy · muscular dystrophy-dystroglycanopathy

Data availability: 69 ClinVar variants · 3 GenCC gene-disease records.

Disease family

An umbrella term covering 7 Mondo subtypes.

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

Related subtypes (22): Ullrich congenital muscular dystrophy, Bethlem myopathy, arthrogryposis due to muscular dystrophy, congenital muscular dystrophy-infantile cataract-hypogonadism syndrome, muscular dystrophy, congenital, with rapid progression, congenital myasthenic syndrome 10, megaconial type congenital muscular dystrophy, congenital muscular dystrophy 1B, congenital merosin-deficient muscular dystrophy 1A, congenital muscular dystrophy due to integrin alpha-7 deficiency, congenital muscular dystrophy due to LMNA mutation, congenital muscular dystrophy-respiratory failure-skin abnormalities-joint hyperlaxity syndrome, congenital myopathy, Paradas type, autosomal recessive myogenic arthrogryposis multiplex congenita, congenital muscular dystrophy with hyperlaxity, muscle-eye-brain disease, rigid spine syndrome, congenital muscular dystrophy with cataracts and intellectual disability, SNUPN-related muscular dystrophy with or without multi-system involvement, congenital muscular dystrophy caused by variation in POMGNT2, collagen 6-related congenital muscular dystrophy, congenital muscular dystrophy without intellectual disability

Subtypes (7): muscular dystrophy-dystroglycanopathy, type A, muscular dystrophy-dystroglycanopathy, type B, muscular dystrophy-dystroglycanopathy, type C, DPM3-congenital disorder of glycosylation, congenital muscular dystrophy with intellectual disability and severe epilepsy, congenital muscular dystrophy with intellectual disability, muscle-eye-brain disease with bilateral multicystic leucodystrophy

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

69 retrieved; paginated sample, class counts are floors:

26 pathogenic/likely pathogenic, 20 conflicting classifications of pathogenicity, 11 pathogenic, 7 uncertain significance, 5 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
578921	NM_152490.5(B3GALNT2):c.448C>T (p.Arg150Ter)	B3GALNT2	Pathogenic	criteria provided, multiple submitters, no conflicts
435529	NM_001101426.4(CRPPA):c.165dup (p.Cys56fs)	CRPPA	Pathogenic	criteria provided, single submitter
4221	NM_024301.5(FKRP):c.826C>A (p.Leu276Ile)	FKRP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4223	NM_024301.5(FKRP):c.1486T>A (p.Ter496Arg)	FKRP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
60543	NM_021971.4(GMPPB):c.553C>T (p.Arg185Cys)	GMPPB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
60545	NM_021971.4(GMPPB):c.860G>A (p.Arg287Gln)	GMPPB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
60547	NM_021971.4(GMPPB):c.988G>A (p.Val330Ile)	GMPPB	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1076645	NM_017739.4(POMGNT1):c.1545del (p.Tyr516fs)	POMGNT1	Pathogenic	criteria provided, multiple submitters, no conflicts
1399654	NM_017739.4(POMGNT1):c.263del (p.Pro88fs)	POMGNT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1450461	NM_017739.4(POMGNT1):c.617G>A (p.Trp206Ter)	POMGNT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1451968	NM_017739.4(POMGNT1):c.563_564del (p.Thr188fs)	POMGNT1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2412674	NM_017739.4(POMGNT1):c.303_304insT (p.Glu102Ter)	POMGNT1	Pathogenic	criteria provided, single submitter
265399	NM_017739.4(POMGNT1):c.636C>T (p.Phe212=)	POMGNT1	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
3993	NM_017739.4(POMGNT1):c.932G>A (p.Arg311Gln)	POMGNT1	Pathogenic/Likely 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
4056486	Single allele	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
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
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
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
3992	NM_017739.4(POMGNT1):c.1324C>T (p.Arg442Cys)	TSPAN1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 30 · Orphanet: 29 · 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
FKRP	Definitive	Autosomal recessive	autosomal recessive limb-girdle muscular dystrophy type 2I	15
FKTN	Definitive	Autosomal recessive	muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4	13
B3GNT2	Moderate	Autosomal recessive	muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A13	2

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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
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
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
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
CRPPA	Orphanet:352479	ISPD-related limb-girdle muscular dystrophy R20
CRPPA	Orphanet:370980	Congenital muscular dystrophy without intellectual disability
CRPPA	Orphanet:588	Muscle-eye-brain disease
CRPPA	Orphanet:899	Walker-Warburg syndrome

Cohort genes → proteins

8 cohort genes, 8 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	8

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
FKRP	HGNC:17997	ENSG00000181027	Q9H9S5	Ribitol 5-phosphate transferase FKRP	gencc,clinvar
FKTN	HGNC:3622	ENSG00000106692	O75072	Ribitol-5-phosphate transferase FKTN	gencc,clinvar
B3GNT2	HGNC:15629	ENSG00000170340	Q9NY97	N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase 2	gencc
POMGNT1	HGNC:19139	ENSG00000085998	Q8WZA1	Protein O-linked-mannose beta-1,2-N-acetylglucosaminyltransferase 1	clinvar
TSPAN1	HGNC:20657	ENSG00000117472	O60635	Tetraspanin-1	clinvar
GMPPB	HGNC:22932	ENSG00000173540	Q9Y5P6	Mannose-1-phosphate guanylyltransferase catalytic subunit beta	clinvar
B3GALNT2	HGNC:28596	ENSG00000162885	Q8NCR0	UDP-GalNAc:beta-1,3-N-acetylgalactosaminyltransferase 2	clinvar
CRPPA	HGNC:37276	ENSG00000214960	A4D126	D-ribitol-5-phosphate cytidylyltransferase	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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…
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…
B3GNT2	N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase 2	Beta-1,3-N-acetylglucosaminyltransferase involved in the synthesis of poly-N-acetyllactosamine.
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.
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.
CRPPA	D-ribitol-5-phosphate cytidylyltransferase	Cytidylyltransferase required for protein O-linked mannosylation.

Protein-family classification

Druggable: 4 · Difficult: 0 · Unknown: 4 · 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)	4	6.0×	0.005
Other/Unknown	4	0.9×	0.755

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FKRP	Other/Unknown	no		LicD/FKTN/FKRP_NTP_transf, LicD_transferase, FKRP_N
FKTN	Other/Unknown	no		LicD/FKTN/FKRP_NTP_transf, FKTN/MNN-like, FKTN_N
B3GNT2	Other/Unknown	no		Glyco_trans_31
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
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
CRPPA	Enzyme (other)	yes	2.7.7.40	ISPD_synthase_CS, Nucleotide-diphossugar_trans, IspD/TarI

Expression context

Cohort genes with no expression data: 0.

6 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)	8
unknown	0

Top tissues across cohort

Tissue	Cohort genes
adrenal tissue	2
calcaneal tendon	2
adenohypophysis	2
mucosa of transverse colon	2
body of pancreas	2
cardiac muscle of right atrium	1
hindlimb stylopod muscle	1
left ventricle myocardium	1
germinal epithelium of ovary	1
oocyte	1
secondary oocyte	1
visceral pleura	1
C1 segment of cervical spinal cord	1
apex of heart	1
bronchial epithelial cell	1
epithelium of bronchus	1
skeletal muscle tissue	1
corpus callosum	1
male germ line stem cell (sensu Vertebrata) in testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FKRP	230	ubiquitous	marker	left ventricle myocardium, cardiac muscle of right atrium, hindlimb stylopod muscle
FKTN	277	ubiquitous	yes	calcaneal tendon, adrenal tissue, germinal epithelium of ovary
B3GNT2	272	ubiquitous	marker	secondary oocyte, oocyte, visceral pleura
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
GMPPB	172	ubiquitous	marker	body of pancreas, adenohypophysis, mucosa of transverse colon
B3GALNT2	141	ubiquitous	marker	body of pancreas, skeletal muscle tissue, adrenal tissue
CRPPA	134	ubiquitous	yes	corpus callosum, male germ line stem cell (sensu Vertebrata) in testis, calcaneal tendon

Protein interactions among cohort

Intra-cohort edges: 15.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GMPPB	2,559
B3GNT2	1,709
CRPPA	1,629
FKRP	1,436
FKTN	1,226
POMGNT1	1,164
TSPAN1	949
B3GALNT2	748

Intra-cohort edges

A	B	Sources
B3GALNT2	CRPPA	string_interaction
B3GALNT2	FKRP	string_interaction
B3GALNT2	FKTN	string_interaction
B3GALNT2	GMPPB	string_interaction
B3GALNT2	POMGNT1	string_interaction
CRPPA	FKRP	string_interaction
CRPPA	FKTN	string_interaction
CRPPA	GMPPB	string_interaction
CRPPA	POMGNT1	string_interaction
FKRP	FKTN	intact, string_interaction
FKRP	GMPPB	string_interaction
FKRP	POMGNT1	string_interaction
FKTN	GMPPB	string_interaction
FKTN	POMGNT1	intact, string_interaction
GMPPB	POMGNT1	string_interaction

Structural data

PDB: 5 · AlphaFold-only: 3 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
B3GNT2	Q9NY97	12
POMGNT1	Q8WZA1	10
FKRP	Q9H9S5	8
GMPPB	Q9Y5P6	3
CRPPA	A4D126	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
FKTN	O75072	92.48
TSPAN1	O60635	88.31
B3GALNT2	Q8NCR0	86.81

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 15. Enrichment computed across 8 evidence-associated genes (7 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 7 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	466.1×	7e-10	FKRP, FKTN, POMGNT1, CRPPA
Defective POMGNT1 causes MDDGA3, MDDGB3 and MDDGC3	1	815.7×	0.006	POMGNT1
O-linked glycosylation	2	41.3×	0.006	B3GNT2, B3GALNT2
DAG1 core M1 glycosylations	1	407.9×	0.008	POMGNT1
DAG1 core M2 glycosylations	1	326.3×	0.008	POMGNT1
Synthesis of GDP-mannose	1	271.9×	0.008	GMPPB
DAG1 core M3 glycosylations	1	271.9×	0.008	B3GALNT2
Keratan sulfate/keratin metabolism	1	70.9×	0.026	B3GNT2
Keratan sulfate biosynthesis	1	54.4×	0.030	B3GNT2
Glycosaminoglycan metabolism	1	31.4×	0.047	B3GNT2
O-linked glycosylation of mucins	1	26.3×	0.051	B3GNT2
Post-translational protein modification	2	5.5×	0.060	B3GNT2, B3GALNT2
Metabolism of carbohydrates and carbohydrate derivatives	1	17.2×	0.066	B3GNT2
Metabolism of proteins	2	3.5×	0.112	B3GNT2, B3GALNT2
Metabolism	1	1.7×	0.468	B3GNT2

GO biological processes 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.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
protein O-linked glycosylation via mannose	4	468.1×	4e-09	FKRP, FKTN, POMGNT1, CRPPA
protein O-linked glycosylation	4	112.3×	8e-07	FKTN, B3GNT2, POMGNT1, B3GALNT2
basement membrane organization	3	191.5×	8e-06	FKRP, FKTN, POMGNT1
localization of cell	2	702.2×	5e-05	FKRP, POMGNT1
skeletal muscle fiber differentiation	2	421.3×	1e-04	FKRP, FKTN
pentitol metabolic process	1	2106.5×	0.004	FKRP
filtration diaphragm assembly	1	2106.5×	0.004	FKRP
pentose metabolic process	1	1053.2×	0.007	FKRP
obsolete GDP-mannose biosynthetic process from mannose	1	702.2×	0.010	GMPPB
creatine metabolic process	1	526.6×	0.010	FKRP
connective tissue development	1	526.6×	0.010	FKRP
oxygen metabolic process	1	526.6×	0.010	FKRP
maintenance of protein localization in endoplasmic reticulum	1	421.3×	0.011	FKRP
GDP-mannose biosynthetic process	1	351.1×	0.011	GMPPB
GDP-mannose metabolic process	1	351.1×	0.011	GMPPB
connective tissue replacement	1	300.9×	0.011	FKRP
reactive gliosis	1	300.9×	0.011	POMGNT1
axon guidance	2	22.6×	0.011	B3GNT2, CRPPA
cerebellar cortex development	1	263.3×	0.012	FKTN
poly-N-acetyllactosamine biosynthetic process	1	263.3×	0.012	B3GNT2
diaphragm development	1	234.1×	0.012	FKRP
isoprenoid biosynthetic process	1	210.7×	0.013	CRPPA
protein import	1	210.7×	0.013	FKRP
response to alcohol	1	191.5×	0.013	FKRP
reelin-mediated signaling pathway	1	150.5×	0.016	FKRP
keratan sulfate proteoglycan biosynthetic process	1	123.9×	0.019	B3GNT2
respiratory system process	1	117.0×	0.019	FKRP
glial cell differentiation	1	110.9×	0.019	FKRP
skeletal muscle tissue regeneration	1	110.9×	0.019	FKRP
dentate gyrus development	1	78.0×	0.025	POMGNT1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 8

Druggability breadth: 2 of 8 evidence-associated genes (25%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FKRP	0	0
FKTN	0	0
B3GNT2	0	0
POMGNT1	0	0
TSPAN1	0	0
GMPPB	0	0
B3GALNT2	0	0
CRPPA	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 4.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
B3GNT2	1	Binding:1
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
GMPPB	2.7.7.13	mannose-1-phosphate guanylyltransferase
B3GALNT2	2.4.1.313	protein O-mannose beta-1,3-N-acetylgalactosaminyltransferase
CRPPA	2.7.7.40	D-ribitol-5-phosphate cytidylyltransferase

Pharmacogenomics

Cohort genes with a PharmGKB record: 8; 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	3	POMGNT1, GMPPB, CRPPA
D	Druggable family + AlphaFold only, no drug	1	B3GALNT2
E	Difficult family or no structure, no drug	4	FKRP, FKTN, B3GNT2, TSPAN1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
FKRP	0	—
FKTN	0	—
B3GNT2	1	—
POMGNT1	1	—
TSPAN1	0	—
GMPPB	0	—
B3GALNT2	0	—
CRPPA	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.