muscular dystrophy-dystroglycanopathy, type A
diseaseOn this page
Also known as cerebroocular dysgenesiscerebroocular dysplasia muscular dystrophy syndromeChemke syndromehard +/- E syndromehard syndromehydrocephalus, agyria and retinal dysplasiahydrocephalus-agyria-retinal dysplasia syndromePagon syndromeWalker-Warburg muscular dystrophyWalker-Warburg syndromeWarburg syndromeWWS
Summary
muscular dystrophy-dystroglycanopathy, type A (MONDO:0000171) is a disease (an umbrella term covering 14 Mondo subtypes) with 18 cohort genes and 1 clinical trial. The dominant Reactome pathway is Matriglycan biosynthesis on DAG1 (8 cohort genes).
At a glance
- Prevalence: 1-9 / 1 000 000 (Europe) [Orphanet-validated]
- Umbrella term: 14 Mondo subtypes
- Cohort genes: 18
- ClinVar variants: 2,643
- Phenotypes (HPO): 51
- Clinical trials: 1
Clinical features
Epidemiology
Prevalence records
4 prevalence record(s), Orphanet:
| Type | Class | Value | Geography | Validation |
|---|---|---|---|---|
| Point prevalence | 1-9 / 1 000 000 | Europe | Validated | |
| Prevalence at birth | 1-9 / 100 000 | 1.65 | Europe | Validated |
| Point prevalence | <1 / 1 000 000 | 0.03 | United Kingdom | Validated |
| Prevalence at birth | 1-9 / 100 000 | 1.2 | Italy | Validated |
Signs & symptoms
Clinical features (HPO)
51 HPO clinical features (Orphanet curated; top 50 by frequency):
| HPO ID | Term | Frequency |
|---|---|---|
| HP:0001284 | Areflexia | Very frequent (80-99%) |
| HP:0001302 | Pachygyria | Very frequent (80-99%) |
| HP:0001321 | Cerebellar hypoplasia | Very frequent (80-99%) |
| HP:0001324 | Muscle weakness | Very frequent (80-99%) |
| HP:0001328 | Specific learning disability | Very frequent (80-99%) |
| HP:0001339 | Lissencephaly | Very frequent (80-99%) |
| HP:0001460 | Aplasia/Hypoplasia involving the skeletal musculature | Very frequent (80-99%) |
| HP:0002119 | Ventriculomegaly | Very frequent (80-99%) |
| HP:0002126 | Polymicrogyria | Very frequent (80-99%) |
| HP:0002269 | Abnormality of neuronal migration | Very frequent (80-99%) |
| HP:0002334 | Abnormality of the cerebellar vermis | Very frequent (80-99%) |
| HP:0002536 | Abnormal cortical gyration | Very frequent (80-99%) |
| HP:0003202 | Skeletal muscle atrophy | Very frequent (80-99%) |
| HP:0003560 | Muscular dystrophy | Very frequent (80-99%) |
| HP:0007731 | Chorioretinal dysplasia | Very frequent (80-99%) |
| HP:0007973 | Retinal dysplasia | Very frequent (80-99%) |
| HP:0010508 | Metatarsus valgus | Very frequent (80-99%) |
| HP:0012400 | Abnormal aldolase level | Very frequent (80-99%) |
| HP:0040081 | Abnormal circulating creatine kinase concentration | Very frequent (80-99%) |
| HP:0045040 | Abnormal lactate dehydrogenase activity | Very frequent (80-99%) |
| HP:0000238 | Hydrocephalus | Very frequent (80-99%) |
| HP:0000541 | Retinal detachment | Very frequent (80-99%) |
| HP:0000556 | Retinal dystrophy | Very frequent (80-99%) |
| HP:0000587 | Abnormal optic nerve morphology | Very frequent (80-99%) |
| HP:0000648 | Optic atrophy | Very frequent (80-99%) |
| HP:0001249 | Intellectual disability | Very frequent (80-99%) |
| HP:0001252 | Hypotonia | Very frequent (80-99%) |
| HP:0001263 | Global developmental delay | Very frequent (80-99%) |
| HP:0001265 | Hyporeflexia | Very frequent (80-99%) |
| HP:0000028 | Cryptorchidism | Frequent (30-79%) |
| HP:0000256 | Macrocephaly | Frequent (30-79%) |
| HP:0000501 | Glaucoma | Frequent (30-79%) |
| HP:0000528 | Anophthalmia | Frequent (30-79%) |
| HP:0000568 | Microphthalmia | Frequent (30-79%) |
| HP:0001274 | Agenesis of corpus callosum | Frequent (30-79%) |
| HP:0001305 | Dandy-Walker malformation | Frequent (30-79%) |
| HP:0001331 | Absent septum pellucidum | Frequent (30-79%) |
| HP:0007957 | Corneal opacity | Frequent (30-79%) |
| HP:0008736 | Hypoplasia of penis | Frequent (30-79%) |
| HP:0000175 | Cleft palate | Occasional (5-29%) |
| HP:0000176 | Submucous cleft hard palate | Occasional (5-29%) |
| HP:0000193 | Bifid uvula | Occasional (5-29%) |
| HP:0000252 | Microcephaly | Occasional (5-29%) |
| HP:0000358 | Posteriorly rotated ears | Occasional (5-29%) |
| HP:0000369 | Low-set ears | Occasional (5-29%) |
| HP:0000411 | Protruding ear | Occasional (5-29%) |
| HP:0000482 | Microcornea | Occasional (5-29%) |
| HP:0000518 | Cataract | Occasional (5-29%) |
| HP:0000612 | Iris coloboma | Occasional (5-29%) |
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | muscular dystrophy-dystroglycanopathy, type A |
| Mondo ID | MONDO:0000171 |
| MeSH | D058494 |
| OMIM | 236670 |
| Orphanet | 899 |
| DOID | DOID:0050560 |
| NCIT | C99109 |
| SNOMED CT | 111504002 |
| UMLS | C0265221 |
| MedGen | 75553 |
| GARD | 0002599 |
| Is cancer (heuristic) | no |
Also known as: cerebroocular dysgenesis · cerebroocular dysplasia muscular dystrophy syndrome · Chemke syndrome · hard +/- E syndrome · hard syndrome · hydrocephalus, agyria and retinal dysplasia · hydrocephalus-agyria-retinal dysplasia syndrome · Pagon syndrome · Walker-Warburg muscular dystrophy · Walker-Warburg syndrome · Warburg syndrome · WWS
Data availability: 2,643 ClinVar variants · 14 GenCC gene-disease records · 5 cell lines.
Disease family
An umbrella term covering 14 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 › muscular dystrophy-dystroglycanopathy, type A
Related subtypes (6): 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
Subtypes (14): muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1, muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A3, muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4, muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2, muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A5, muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A6, muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7, muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8, muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 10, muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 11, muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12, muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A13, muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A14, muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9
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:
276 uncertain significance, 227 likely benign, 39 pathogenic, 20 pathogenic/likely pathogenic, 17 conflicting classifications of pathogenicity, 9 likely pathogenic, 8 benign/likely benign, 4 benign
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1068020 | NM_024301.5(FKRP):c.229C>T (p.Gln77Ter) | FKRP | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1068850 | NM_024301.5(FKRP):c.515dup (p.Asn172fs) | FKRP | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1071118 | NM_024301.5(FKRP):c.540_570dup (p.Cys191fs) | FKRP | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1071721 | NC_000019.9:g.(?47258698)(47260205_?)del | FKRP | Pathogenic | criteria provided, single submitter |
| 1071722 | NC_000019.9:g.(?_47255735)_47259271del | FKRP | Pathogenic | criteria provided, single submitter |
| 1072037 | NM_024301.5(FKRP):c.919del (p.Tyr307fs) | FKRP | Pathogenic | criteria provided, single submitter |
| 1072163 | NM_024301.5(FKRP):c.1A>C (p.Met1Leu) | FKRP | Pathogenic | criteria provided, single submitter |
| 1072170 | NM_024301.5(FKRP):c.947_948insA (p.Cys317fs) | FKRP | Pathogenic | criteria provided, single submitter |
| 1073047 | NM_024301.5(FKRP):c.511_523del (p.Leu171fs) | FKRP | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1075782 | NM_024301.5(FKRP):c.661dup (p.Ser221fs) | FKRP | Pathogenic | criteria provided, single submitter |
| 1076575 | NM_024301.5(FKRP):c.979dup (p.Arg327fs) | FKRP | Pathogenic | criteria provided, single submitter |
| 1180605 | NM_024301.5(FKRP):c.1012G>C (p.Val338Leu) | FKRP | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1180733 | NM_024301.5(FKRP):c.1034G>C (p.Gly345Ala) | FKRP | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1358348 | NM_024301.5(FKRP):c.998_1015del (p.Leu333_Val338del) | FKRP | Pathogenic | criteria provided, single submitter |
| 1363110 | NM_024301.5(FKRP):c.1335_1336del (p.Leu446fs) | FKRP | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1363219 | NM_024301.5(FKRP):c.650dup (p.Val218fs) | FKRP | Pathogenic | criteria provided, single submitter |
| 1365203 | NM_024301.5(FKRP):c.892G>T (p.Gly298Ter) | FKRP | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1376288 | NM_024301.5(FKRP):c.1075del (p.Trp359fs) | FKRP | Pathogenic | criteria provided, single submitter |
| 1378149 | NM_024301.5(FKRP):c.1354del (p.Leu452fs) | FKRP | Pathogenic | criteria provided, single submitter |
| 1395158 | NM_024301.5(FKRP):c.1187dup (p.Ala397fs) | FKRP | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1451632 | NM_024301.5(FKRP):c.224del (p.Pro75fs) | FKRP | Pathogenic | criteria provided, single submitter |
| 1452093 | NM_024301.5(FKRP):c.779_785del (p.Glu260fs) | FKRP | Pathogenic | criteria provided, single submitter |
| 1452218 | NM_024301.5(FKRP):c.1253G>A (p.Trp418Ter) | FKRP | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1455089 | NM_024301.5(FKRP):c.151G>T (p.Val51Phe) | FKRP | Pathogenic | criteria provided, single submitter |
| 1459886 | NC_000019.9:g.(?47255735)(47259270_?)del | FKRP | Pathogenic | criteria provided, single submitter |
| 1487439 | NM_024301.5(FKRP):c.877A>G (p.Thr293Ala) | FKRP | Pathogenic | criteria provided, single submitter |
| 1063728 | NM_001079802.2(FKTN):c.1198_1207del (p.Cys400fs) | FKTN | Pathogenic | criteria provided, single submitter |
| 1068744 | NM_001079802.2(FKTN):c.1022del (p.Pro341fs) | FKTN | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1070267 | NC_000009.11:g.(?108337304)(108397555_?)del | FKTN | Pathogenic | criteria provided, single submitter |
| 1070650 | NM_001079802.2(FKTN):c.914G>A (p.Trp305Ter) | FKTN | Pathogenic | criteria provided, single submitter |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 132 · Orphanet: 60 · 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 |
| CRPPA | Definitive | Autosomal recessive | muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7 | 7 |
| DAG1 | Definitive | Autosomal recessive | autosomal recessive limb-girdle muscular dystrophy type 2P | 8 |
| 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 |
| LARGE1 | Definitive | Autosomal recessive | muscular dystrophy-dystroglycanopathy type B6 | 6 |
| POMGNT1 | Definitive | Autosomal recessive | muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A3 | 17 |
| POMGNT2 | Definitive | Autosomal recessive | muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8 | 6 |
| POMK | Definitive | Autosomal recessive | muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12 | 9 |
| 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 | muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 10 | 5 |
| B4GAT1 | Strong | Autosomal recessive | muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A13 | 3 |
| COL4A1 | Supportive | Autosomal recessive | muscular dystrophy-dystroglycanopathy, type A | 11 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| 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 |
| 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 |
| B4GAT1 | 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 |
| 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 |
| COL4A1 | Orphanet:36383 | COL4A1/2-related familial vascular leukoencephalopathy |
| COL4A1 | Orphanet:477749 | Pontine autosomal dominant microangiopathy with leukoencephalopathy |
| COL4A1 | Orphanet:481986 | Familial schizencephaly |
| COL4A1 | Orphanet:73229 | HANAC syndrome |
| COL4A1 | Orphanet:75326 | Familial isolated retinal arteriolar tortuosity |
| COL4A1 | Orphanet:899 | Walker-Warburg syndrome |
| COL4A1 | Orphanet:99810 | Familial porencephaly |
| POMGNT2 | Orphanet:899 | Walker-Warburg syndrome |
| POMK | Orphanet:370959 | Congenital muscular dystrophy with cerebellar involvement |
| POMK | Orphanet:445110 | Limb-girdle muscular dystrophy due to POMK deficiency |
| POMK | Orphanet:899 | Walker-Warburg syndrome |
| DAG1 | Orphanet:206599 | Isolated asymptomatic elevation of creatine phosphokinase |
| DAG1 | Orphanet:280333 | Alpha-dystroglycan-related limb-girdle muscular dystrophy R16 |
| DAG1 | Orphanet:370997 | Muscle-eye-brain disease with bilateral multicystic leucodystrophy |
| DAG1 | Orphanet:899 | Walker-Warburg syndrome |
| 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 |
Cohort genes → proteins
18 cohort genes, 18 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 18 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| RXYLT1 | HGNC:13530 | ENSG00000118600 | Q9Y2B1 | Ribitol-5-phosphate xylosyltransferase 1 | gencc,clinvar |
| FKRP | HGNC:17997 | ENSG00000181027 | Q9H9S5 | Ribitol 5-phosphate transferase FKRP | gencc,clinvar |
| FKTN | HGNC:3622 | ENSG00000106692 | O75072 | Ribitol-5-phosphate transferase FKTN | gencc,clinvar |
| POMT1 | HGNC:9202 | ENSG00000130714 | Q9Y6A1 | Protein O-mannosyl-transferase 1 | gencc,clinvar |
| B4GAT1 | HGNC:15685 | ENSG00000174684 | O43505 | Beta-1,4-glucuronyltransferase 1 | gencc |
| POMGNT1 | HGNC:19139 | ENSG00000085998 | Q8WZA1 | Protein O-linked-mannose beta-1,2-N-acetylglucosaminyltransferase 1 | gencc |
| POMT2 | HGNC:19743 | ENSG00000009830 | Q9UKY4 | Protein O-mannosyl-transferase 2 | gencc |
| COL4A1 | HGNC:2202 | ENSG00000187498 | P02462 | Collagen alpha-1(IV) chain | gencc |
| POMGNT2 | HGNC:25902 | ENSG00000144647 | Q8NAT1 | Protein O-linked-mannose beta-1,4-N-acetylglucosaminyltransferase 2 | gencc |
| POMK | HGNC:26267 | ENSG00000185900 | Q9H5K3 | Protein O-mannose kinase | gencc |
| DAG1 | HGNC:2666 | ENSG00000173402 | Q14118 | Dystroglycan 1 | gencc |
| B3GALNT2 | HGNC:28596 | ENSG00000162885 | Q8NCR0 | UDP-GalNAc:beta-1,3-N-acetylgalactosaminyltransferase 2 | gencc |
| CRPPA | HGNC:37276 | ENSG00000214960 | A4D126 | D-ribitol-5-phosphate cytidylyltransferase | gencc |
| LARGE1 | HGNC:6511 | ENSG00000133424 | O95461 | Xylosyl- and glucuronyltransferase LARGE1 | gencc |
| CALM3 | HGNC:1449 | ENSG00000160014 | P0DP25 | Calmodulin-3 | clinvar |
| CELSR1 | HGNC:1850 | ENSG00000075275 | Q9NYQ6 | Cadherin EGF LAG seven-pass G-type receptor 1 | clinvar |
| PLPP7 | HGNC:28174 | ENSG00000160539 | Q8NBV4 | Inactive phospholipid phosphatase 7 | clinvar |
| ABCA1 | HGNC:29 | ENSG00000165029 | O95477 | Phospholipid-transporting ATPase ABCA1 | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| 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… |
| 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. |
| B4GAT1 | Beta-1,4-glucuronyltransferase 1 | Beta-1,4-glucuronyltransferase involved in O-mannosylation of alpha-dystroglycan (DAG1). |
| 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. |
| POMT2 | Protein O-mannosyl-transferase 2 | Transfers mannosyl residues to the hydroxyl group of serine or threonine residues. |
| COL4A1 | Collagen alpha-1(IV) chain | Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a ‘chicken-wire’ meshwork together with laminins, proteoglycans and entactin/nidogen. |
| POMGNT2 | Protein O-linked-mannose beta-1,4-N-acetylglucosaminyltransferase 2 | O-linked mannose beta-1,4-N-acetylglucosaminyltransferase that transfers UDP-N-acetyl-D-glucosamine to the 4-position of the mannose to generate N-acetyl-D-glucosamine-beta-1,4-O-D-mannosylprotein. |
| POMK | Protein O-mannose kinase | Protein O-mannose kinase that specifically mediates phosphorylation at the 6-position of an O-mannose of the trisaccharide (N-acetylgalactosamine (GalNAc)-beta-1,3-N-acetylglucosamine (GlcNAc)-beta-1,4-mannose) to generate phosphorylated O… |
| DAG1 | Dystroglycan 1 | The dystroglycan complex is involved in a number of signaling events and processes including laminin deposition and extracellular matrix assembly, acetylcholine receptor clustering, sarcolemmal stability, cell survival, peripheral nerve my… |
| 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. |
| LARGE1 | Xylosyl- and glucuronyltransferase LARGE1 | Bifunctional glycosyltransferase with both alpha-1,3-xylosyltransferase and beta-1,3-glucuronyltransferase activities involved in the maturation of alpha-dystroglycan (DAG1) by glycosylation leading to DAG1 binding to laminin G-like domain… |
| CALM3 | Calmodulin-3 | Calmodulin acts as part of a calcium signal transduction pathway by mediating the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding. |
| CELSR1 | Cadherin EGF LAG seven-pass G-type receptor 1 | Receptor that may have an important role in cell/cell signaling during nervous system formation. |
| PLPP7 | Inactive phospholipid phosphatase 7 | Plays a role as negative regulator of myoblast differentiation, in part through effects on MTOR signaling. |
| ABCA1 | Phospholipid-transporting ATPase ABCA1 | Catalyzes the translocation of specific phospholipids from the cytoplasmic to the extracellular/lumenal leaflet of membrane coupled to the hydrolysis of ATP. |
Protein-family classification
Druggable: 13 · Difficult: 0 · Unknown: 5 · Druggable fraction: 0.72
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) | 8 | 5.3× | 3e-04 |
| Antibody/Immunoglobulin | 2 | 3.2× | 0.375 |
| Transporter | 1 | 4.3× | 0.416 |
| Kinase | 1 | 1.5× | 0.643 |
| GPCR | 1 | 1.3× | 0.643 |
| Other/Unknown | 5 | 0.5× | 0.996 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| 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 | |
| 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 |
| B4GAT1 | Enzyme (other) | yes | 2.4.1.149 | B4GAT1 |
| POMGNT1 | Enzyme (other) | yes | 2.4.1.312 | Glyco_trans_13, Nucleotide-diphossugar_trans, POMGNT1_PANDER-like |
| POMT2 | Enzyme (other) | yes | 2.4.1.109 | ArnT-like_N, MIR_motif, PMT-like |
| COL4A1 | Other/Unknown | no | Collagen_IV_NC, Collagen, CTDL_fold | |
| POMGNT2 | Antibody/Immunoglobulin | yes | 2.4.1.312 | FN3_dom, Glycosyltransferase_61, Ig-like_fold |
| POMK | Kinase | yes | 2.7.1.183 | Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Kinase-like_dom_sf |
| DAG1 | Antibody/Immunoglobulin | yes | Cadg, DAG1_C, Ig-like_fold | |
| 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 |
| LARGE1 | Enzyme (other) | yes | 2.4.1.B80 | Glyco_trans_8, Nucleotide-diphossugar_trans, Xyl/GlcA_transferase |
| CALM3 | Other/Unknown | no | EF_hand_dom, EF-hand-dom_pair, EF_Hand_1_Ca_BS | |
| CELSR1 | GPCR | yes | EGF-type_Asp/Asn_hydroxyl_site, GPS, EGF | |
| PLPP7 | Other/Unknown | no | PAP2/HPO, PAP2/HPO_sf | |
| ABCA1 | Transporter | yes | ABC_transporter-like_ATP-bd, AAA+_ATPase, ABC2_TM |
Expression context
Cohort genes with no expression data: 0.
13 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) | 18 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| adrenal tissue | 3 |
| apex of heart | 3 |
| cardiac muscle of right atrium | 2 |
| hindlimb stylopod muscle | 2 |
| calcaneal tendon | 2 |
| right hemisphere of cerebellum | 2 |
| middle temporal gyrus | 2 |
| left testis | 2 |
| caput epididymis | 1 |
| corpus epididymis | 1 |
| cranial nerve II | 1 |
| left ventricle myocardium | 1 |
| germinal epithelium of ovary | 1 |
| cerebellar cortex | 1 |
| cerebellar hemisphere | 1 |
| endothelial cell | 1 |
| pons | 1 |
| C1 segment of cervical spinal cord | 1 |
| adenohypophysis | 1 |
| right testis | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| 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 |
| FKTN | 277 | ubiquitous | yes | calcaneal tendon, adrenal tissue, germinal epithelium of ovary |
| POMT1 | 264 | ubiquitous | marker | right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex |
| B4GAT1 | 285 | ubiquitous | marker | endothelial cell, middle temporal gyrus, pons |
| POMGNT1 | 269 | ubiquitous | marker | apex of heart, C1 segment of cervical spinal cord, adenohypophysis |
| POMT2 | 222 | ubiquitous | yes | right testis, left testis, testis |
| COL4A1 | 283 | ubiquitous | marker | visceral pleura, placenta, right coronary artery |
| POMGNT2 | 245 | ubiquitous | marker | lateral nuclear group of thalamus, right hemisphere of cerebellum, cardiac muscle of right atrium |
| POMK | 289 | ubiquitous | yes | paraflocculus, middle temporal gyrus, Brodmann (1909) area 10 |
| DAG1 | 299 | ubiquitous | marker | olfactory bulb, trigeminal ganglion, dorsal root ganglion |
| 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 |
| LARGE1 | 233 | tissue_specific | marker | heart left ventricle, cardiac ventricle, apex of heart |
| CALM3 | 297 | ubiquitous | marker | prefrontal cortex, right frontal lobe, left testis |
| CELSR1 | 224 | ubiquitous | marker | ventricular zone, lower esophagus mucosa, bronchial epithelial cell |
| PLPP7 | 195 | ubiquitous | yes | apex of heart, hindlimb stylopod muscle, gastrocnemius |
| ABCA1 | 272 | ubiquitous | marker | adrenal tissue, skin of hip, left adrenal gland |
Protein interactions among cohort
Intra-cohort edges: 74.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| ABCA1 | 3,551 |
| COL4A1 | 2,909 |
| DAG1 | 2,301 |
| CRPPA | 1,629 |
| POMT1 | 1,475 |
| FKRP | 1,436 |
| POMT2 | 1,284 |
| POMK | 1,251 |
| FKTN | 1,226 |
| CELSR1 | 1,166 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| B3GALNT2 | B4GAT1 | string_interaction |
| B3GALNT2 | CRPPA | string_interaction |
| B3GALNT2 | FKRP | string_interaction |
| B3GALNT2 | FKTN | string_interaction |
| B3GALNT2 | LARGE1 | string_interaction |
| B3GALNT2 | POMGNT1 | string_interaction |
| B3GALNT2 | POMGNT2 | string_interaction |
| B3GALNT2 | POMK | string_interaction |
| B3GALNT2 | POMT1 | string_interaction |
| B3GALNT2 | POMT2 | string_interaction |
| B3GALNT2 | RXYLT1 | string_interaction |
| B4GAT1 | CRPPA | string_interaction |
| B4GAT1 | DAG1 | string_interaction |
| B4GAT1 | FKRP | biogrid_interaction, intact, string_interaction |
| B4GAT1 | FKTN | biogrid_interaction, intact, string_interaction |
| B4GAT1 | LARGE1 | intact |
| B4GAT1 | POMGNT1 | string_interaction |
| B4GAT1 | POMGNT2 | string_interaction |
| B4GAT1 | POMK | intact, string_interaction |
| B4GAT1 | POMT1 | intact, string_interaction |
| B4GAT1 | POMT2 | string_interaction |
| B4GAT1 | RXYLT1 | string_interaction |
| CRPPA | DAG1 | string_interaction |
| CRPPA | FKRP | string_interaction |
| CRPPA | FKTN | string_interaction |
| CRPPA | LARGE1 | string_interaction |
| CRPPA | POMGNT1 | string_interaction |
| CRPPA | POMGNT2 | string_interaction |
| CRPPA | POMK | string_interaction |
| CRPPA | POMT1 | string_interaction |
| CRPPA | POMT2 | string_interaction |
| CRPPA | RXYLT1 | string_interaction |
| DAG1 | FKRP | string_interaction |
| DAG1 | FKTN | string_interaction |
| DAG1 | LARGE1 | string_interaction |
| DAG1 | POMGNT1 | string_interaction |
| DAG1 | POMT1 | string_interaction |
| DAG1 | POMT2 | string_interaction |
| FKRP | FKTN | intact, string_interaction |
| FKRP | LARGE1 | string_interaction |
| FKRP | POMGNT1 | string_interaction |
| FKRP | POMGNT2 | string_interaction |
| FKRP | POMK | string_interaction |
| FKRP | POMT1 | string_interaction |
| FKRP | POMT2 | string_interaction |
| FKRP | RXYLT1 | intact, string_interaction |
| FKTN | LARGE1 | string_interaction |
| FKTN | POMGNT1 | intact, string_interaction |
| FKTN | POMGNT2 | string_interaction |
| FKTN | POMK | string_interaction |
Structural data
PDB: 10 · AlphaFold-only: 8 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| CALM3 | P0DP25 | 26 |
| POMGNT1 | Q8WZA1 | 10 |
| FKRP | Q9H9S5 | 8 |
| DAG1 | Q14118 | 8 |
| ABCA1 | O95477 | 7 |
| COL4A1 | P02462 | 4 |
| LARGE1 | O95461 | 4 |
| POMGNT2 | Q8NAT1 | 3 |
| CELSR1 | Q9NYQ6 | 2 |
| CRPPA | A4D126 | 1 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| FKTN | O75072 | 92.48 |
| POMK | Q9H5K3 | 91.62 |
| B4GAT1 | O43505 | 88.46 |
| POMT1 | Q9Y6A1 | 88.09 |
| POMT2 | Q9UKY4 | 87.96 |
| B3GALNT2 | Q8NCR0 | 86.81 |
| RXYLT1 | Q9Y2B1 | 85.72 |
| PLPP7 | Q8NBV4 | 80.10 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 55. Enrichment computed across 18 evidence-associated genes (16 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 16 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 | 8 | 407.9× | 3e-19 | RXYLT1, FKRP, FKTN, B4GAT1, POMGNT1, DAG1, CRPPA, LARGE1 |
| DAG1 core M3 glycosylations | 6 | 713.8× | 7e-17 | POMT1, POMT2, POMGNT2, POMK, DAG1, B3GALNT2 |
| DAG1 core M1 glycosylations | 4 | 713.8× | 5e-11 | POMT1, POMGNT1, POMT2, DAG1 |
| DAG1 core M2 glycosylations | 4 | 571.0× | 2e-10 | POMT1, POMGNT1, POMT2, DAG1 |
| Defective POMT2 causes MDDGA2, MDDGB2 and MDDGC2 | 3 | 713.8× | 2e-08 | POMT1, POMT2, DAG1 |
| Defective POMT1 causes MDDGA1, MDDGB1 and MDDGC1 | 3 | 713.8× | 2e-08 | POMT1, POMT2, DAG1 |
| Defective POMGNT1 causes MDDGA3, MDDGB3 and MDDGC3 | 2 | 713.8× | 1e-05 | POMGNT1, DAG1 |
| O-linked glycosylation | 4 | 36.1× | 2e-05 | B4GAT1, POMK, B3GALNT2, LARGE1 |
| Defective LARGE causes MDDGA6 and MDDGB6 | 2 | 475.8× | 3e-05 | B4GAT1, LARGE1 |
| Regulation of CDH1 posttranslational processing and trafficking to plasma membrane | 2 | 42.0× | 0.006 | POMT1, POMT2 |
| Diseases associated with O-glycosylation of proteins | 2 | 26.9× | 0.012 | B4GAT1, LARGE1 |
| Defective ABCA1 causes TGD | 1 | 356.9× | 0.013 | ABCA1 |
| Non-integrin membrane-ECM interactions | 2 | 19.3× | 0.019 | COL4A1, DAG1 |
| ECM proteoglycans | 2 | 18.8× | 0.019 | COL4A1, DAG1 |
| Diseases of glycosylation | 2 | 16.4× | 0.024 | B4GAT1, LARGE1 |
| Post-translational protein modification | 4 | 4.8× | 0.028 | B4GAT1, POMK, B3GALNT2, LARGE1 |
| HDL assembly | 1 | 89.2× | 0.036 | ABCA1 |
| CASP4 inflammasome assembly | 1 | 79.3× | 0.038 | CALM3 |
| Diseases of metabolism | 2 | 10.1× | 0.048 | B4GAT1, LARGE1 |
| Enterobacterial factors antagonize host defense | 1 | 51.0× | 0.053 | CALM3 |
| Anchoring fibril formation | 1 | 47.6× | 0.055 | COL4A1 |
| Plasma lipoprotein assembly | 1 | 44.6× | 0.055 | ABCA1 |
| Scavenging by Class A Receptors | 1 | 37.6× | 0.061 | COL4A1 |
| Fibronectin matrix formation | 1 | 35.7× | 0.061 | COL4A1 |
| Crosslinking of collagen fibrils | 1 | 35.7× | 0.061 | COL4A1 |
| Keratan sulfate/keratin metabolism | 1 | 31.0× | 0.065 | B4GAT1 |
| Attachment of bacteria to epithelial cells | 1 | 31.0× | 0.065 | COL4A1 |
| ABC transporter disorders | 1 | 27.4× | 0.068 | ABCA1 |
| Metabolism of proteins | 4 | 3.1× | 0.068 | B4GAT1, POMK, B3GALNT2, LARGE1 |
| NR1H2 and NR1H3-mediated signaling | 1 | 24.6× | 0.071 | ABCA1 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 18 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 | 10 | 520.1× | 8e-25 | RXYLT1, FKRP, FKTN, POMT1, B4GAT1, POMGNT1, POMT2, POMGNT2 (+2 more) |
| basement membrane organization | 7 | 198.6× | 2e-13 | FKRP, FKTN, POMGNT1, POMT2, COL4A1, DAG1, LARGE1 |
| protein O-linked glycosylation | 8 | 99.9× | 3e-13 | RXYLT1, FKTN, POMT1, POMGNT1, POMGNT2, POMK, B3GALNT2, LARGE1 |
| localization of cell | 3 | 468.1× | 1e-06 | FKRP, POMGNT1, LARGE1 |
| reactive gliosis | 3 | 401.2× | 2e-06 | POMGNT1, POMT2, LARGE1 |
| skeletal muscle fiber differentiation | 3 | 280.9× | 4e-06 | FKRP, FKTN, LARGE1 |
| skeletal muscle tissue regeneration | 3 | 147.8× | 3e-05 | FKRP, DAG1, LARGE1 |
| dentate gyrus development | 3 | 104.0× | 8e-05 | POMGNT1, POMT2, LARGE1 |
| connective tissue development | 2 | 468.1× | 2e-04 | FKRP, LARGE1 |
| neuron migration | 4 | 29.7× | 2e-04 | FKRP, CELSR1, POMGNT2, LARGE1 |
| nerve development | 2 | 104.0× | 0.003 | DAG1, LARGE1 |
| cellular response to cholesterol | 2 | 93.6× | 0.004 | DAG1, ABCA1 |
| positive regulation of Rac protein signal transduction | 2 | 72.0× | 0.006 | DAG1, LARGE1 |
| neuromuscular process | 2 | 58.5× | 0.008 | FKRP, POMK |
| muscle attachment | 1 | 936.2× | 0.010 | DAG1 |
| pentitol metabolic process | 1 | 936.2× | 0.010 | FKRP |
| nerve maturation | 1 | 936.2× | 0.010 | DAG1 |
| post-embryonic hindlimb morphogenesis | 1 | 936.2× | 0.010 | LARGE1 |
| filtration diaphragm assembly | 1 | 936.2× | 0.010 | FKRP |
| obsolete establishment of protein localization to mitochondrial membrane | 1 | 936.2× | 0.010 | CALM3 |
| heart morphogenesis | 2 | 41.6× | 0.010 | FKRP, DAG1 |
| axon guidance | 3 | 15.1× | 0.010 | B4GAT1, DAG1, CRPPA |
| glycoprotein biosynthetic process | 2 | 37.5× | 0.012 | B3GALNT2, LARGE1 |
| brain development | 3 | 13.2× | 0.012 | FKRP, COL4A1, POMK |
| calcium-dependent cell-matrix adhesion | 1 | 468.1× | 0.014 | DAG1 |
| pentose metabolic process | 1 | 468.1× | 0.014 | FKRP |
| response to vitamin B3 | 1 | 468.1× | 0.014 | ABCA1 |
| regulation of high-density lipoprotein particle assembly | 1 | 468.1× | 0.014 | ABCA1 |
| positive regulation of high-density lipoprotein particle assembly | 1 | 468.1× | 0.014 | ABCA1 |
| negative regulation of high voltage-gated calcium channel activity | 1 | 468.1× | 0.014 | CALM3 |
Therapeutics
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 18
Druggability breadth: 5 of 18 evidence-associated genes (28%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| RXYLT1 | 0 | 0 |
| FKRP | 0 | 0 |
| FKTN | 0 | 0 |
| POMT1 | 0 | 0 |
| B4GAT1 | 0 | 0 |
| POMGNT1 | 0 | 0 |
| POMT2 | 0 | 0 |
| COL4A1 | 0 | 0 |
| POMGNT2 | 0 | 0 |
| POMK | 0 | 0 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 10.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| DAG1 | 4 | Binding:4 |
| LARGE1 | 2 | Functional:2 |
| ABCA1 | 2 | Binding:2 |
| POMGNT1 | 1 | Binding:1 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| RXYLT1 | 2.4.2.61 | alpha-dystroglycan beta1,4-xylosyltransferase |
| POMT1 | 2.4.1.109 | dolichyl-phosphate-mannose-protein mannosyltransferase |
| B4GAT1 | 2.4.1.149 | N-acetyllactosaminide beta-1,3-N-acetylglucosaminyltransferase |
| POMGNT1 | 2.4.1.312 | protein O-mannose beta-1,4-N-acetylglucosaminyltransferase |
| POMT2 | 2.4.1.109 | dolichyl-phosphate-mannose-protein mannosyltransferase |
| POMGNT2 | 2.4.1.312 | protein O-mannose beta-1,4-N-acetylglucosaminyltransferase |
| POMK | 2.7.1.183 | glycoprotein-mannosyl O6-kinase |
| B3GALNT2 | 2.4.1.313 | protein O-mannose beta-1,3-N-acetylgalactosaminyltransferase |
| CRPPA | 2.7.7.40 | D-ribitol-5-phosphate cytidylyltransferase |
| LARGE1 | 2.4.1.B80, 2.4.2.B18 | , |
Pharmacogenomics
Cohort genes with a PharmGKB record: 18; 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 | 7 | POMGNT1, POMGNT2, DAG1, CRPPA, LARGE1, CELSR1, ABCA1 |
| D | Druggable family + AlphaFold only, no drug | 6 | RXYLT1, POMT1, B4GAT1, POMT2, POMK, B3GALNT2 |
| E | Difficult family or no structure, no drug | 5 | FKRP, FKTN, COL4A1, CALM3, PLPP7 |
Undrugged target profiles
18 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| RXYLT1 | 0 | — |
| FKRP | 0 | — |
| FKTN | 0 | — |
| POMT1 | 0 | — |
| B4GAT1 | 0 | — |
| POMGNT1 | 1 | — |
| POMT2 | 0 | — |
| COL4A1 | 0 | — |
| POMGNT2 | 0 | — |
| POMK | 0 | — |
| DAG1 | 4 | — |
| B3GALNT2 | 0 | — |
| CRPPA | 0 | — |
| LARGE1 | 2 | — |
| CALM3 | 0 | — |
| CELSR1 | 0 | — |
| PLPP7 | 0 | — |
| ABCA1 | 2 | — |
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 |