Bethlem myopathy 1A
diseaseOn this page
Also known as Bethlem myopathy 1BTHLM1
Summary
Bethlem myopathy 1A (MONDO:0024530) is a disease caused by variants in COL6A1, COL6A3, and COL6A2, with 10 cohort genes and 1 clinical trial. The dominant Reactome pathway is Collagen chain trimerization (4 cohort genes).
At a glance
- Causal genes: COL6A1 (GenCC Definitive), COL6A3 (GenCC Definitive), COL6A2 (GenCC Strong)
- Cohort genes: 10
- ClinVar variants: 6,616
- Clinical trials: 1
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | Bethlem myopathy 1A |
| Mondo ID | MONDO:0024530 |
| OMIM | 158810 |
| DOID | DOID:0061198 |
| GARD | 0025413 |
| Is cancer (heuristic) | no |
Also known as: Bethlem myopathy 1 · BTHLM1
Data availability: 6,616 ClinVar variants · 8 GenCC gene-disease records · 17 cell lines.
Disease family
Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › muscle tissue disorder › skeletal muscle disorder › myopathy › muscular dystrophy › progressive muscular dystrophy › Bethlem myopathy › Bethlem myopathy 1A
Related subtypes (3): Bethlem myopathy 2, Bethlem myopathy 1B, Bethlem myopathy 1C
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:
237 likely benign, 219 uncertain significance, 77 conflicting classifications of pathogenicity, 36 pathogenic, 14 benign, 7 likely pathogenic, 6 benign/likely benign, 4 pathogenic/likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1013195 | NM_001848.3(COL6A1):c.887G>A (p.Gly296Glu) | COL6A1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1072275 | NM_001848.3(COL6A1):c.823G>A (p.Gly275Arg) | COL6A1 | Pathogenic | criteria provided, single submitter |
| 1073810 | NM_001848.3(COL6A1):c.1738del (p.Gln580fs) | COL6A1 | Pathogenic | criteria provided, single submitter |
| 1073927 | NM_001848.3(COL6A1):c.1318G>T (p.Gly440Ter) | COL6A1 | Pathogenic | criteria provided, single submitter |
| 1076562 | NM_001848.3(COL6A1):c.877G>C (p.Gly293Arg) | COL6A1 | Pathogenic | criteria provided, single submitter |
| 1322138 | NM_001848.3(COL6A1):c.1056+1G>C | COL6A1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1322139 | NM_001848.3(COL6A1):c.2197_2200del (p.Asp733fs) | COL6A1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1322141 | NM_001848.3(COL6A1):c.1612-1G>A | COL6A1 | Pathogenic | criteria provided, multiple submitters, no conflicts |
| 1328167 | NM_001848.3(COL6A1):c.824G>A (p.Gly275Glu) | COL6A1 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1374571 | NM_001848.3(COL6A1):c.931G>T (p.Gly311Cys) | COL6A1 | Pathogenic | criteria provided, single submitter |
| 1375454 | NM_001848.3(COL6A1):c.244C>T (p.Arg82Ter) | COL6A1 | Pathogenic | criteria provided, single submitter |
| 1389428 | NM_001848.3(COL6A1):c.1867_1868del (p.Ser623fs) | COL6A1 | Pathogenic | criteria provided, single submitter |
| 1060752 | NM_001849.4(COL6A2):c.2097_2098delinsTA (p.Gly700Ser) | COL6A2 | Pathogenic | criteria provided, single submitter |
| 1061166 | NM_001849.4(COL6A2):c.2832_2927del (p.Phe944_Ala975del) | COL6A2 | Pathogenic | criteria provided, single submitter |
| 1068195 | NM_001849.4(COL6A2):c.1817-2A>G | COL6A2 | Pathogenic/Likely pathogenic | criteria provided, multiple submitters, no conflicts |
| 1068296 | NM_001849.4(COL6A2):c.1053+2T>G | COL6A2 | Pathogenic | criteria provided, single submitter |
| 1070014 | NC_000021.8:g.(?_47529674)_47540994del | COL6A2 | Pathogenic | criteria provided, single submitter |
| 1070015 | NC_000021.8:g.(?_47533070)_47584395del | COL6A2 | Pathogenic | criteria provided, single submitter |
| 1070123 | NM_001849.4(COL6A2):c.2023C>T (p.Gln675Ter) | COL6A2 | Pathogenic | criteria provided, single submitter |
| 1070535 | NM_001849.4(COL6A2):c.999+9_1053+32delinsGCTGAAGGAGGGGTGCAAACGGCCCTTACCCGGTTTCCAGGGTCTCCCTTGCAGCCTTCA | COL6A2 | Pathogenic | criteria provided, single submitter |
| 1071804 | NM_001849.4(COL6A2):c.955-1G>C | COL6A2 | Pathogenic | criteria provided, single submitter |
| 1072953 | NM_001849.4(COL6A2):c.1053+2T>A | COL6A2 | Pathogenic | criteria provided, single submitter |
| 1073260 | NM_001849.4(COL6A2):c.998del (p.Lys333fs) | COL6A2 | Pathogenic | criteria provided, single submitter |
| 1073867 | NM_001849.4(COL6A2):c.954G>C (p.Lys318Asn) | COL6A2 | Pathogenic | criteria provided, single submitter |
| 1073909 | NM_001849.4(COL6A2):c.2560_2569dup (p.Glu857fs) | COL6A2 | Pathogenic | criteria provided, single submitter |
| 1074374 | NM_001849.4(COL6A2):c.1075dup (p.Glu359fs) | COL6A2 | Pathogenic | criteria provided, single submitter |
| 1075831 | NM_001849.4(COL6A2):c.2500_2501del (p.Ile834fs) | COL6A2 | Pathogenic | criteria provided, single submitter |
| 1184919 | NM_001849.4(COL6A2):c.439C>T (p.Gln147Ter) | COL6A2 | Pathogenic | criteria provided, single submitter |
| 1348005 | NM_001849.4(COL6A2):c.821G>A (p.Gly274Asp) | COL6A2 | Pathogenic | criteria provided, single submitter |
| 1351958 | NM_001849.4(COL6A2):c.874G>A (p.Gly292Ser) | COL6A2 | Pathogenic | criteria provided, multiple submitters, no conflicts |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 35 · Orphanet: 42 · 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 |
|---|---|---|---|---|
| COL6A1 | Definitive | Autosomal dominant | Bethlem myopathy 1A | 9 |
| COL6A3 | Definitive | Semidominant | Bethlem myopathy 1A | 15 |
| COL6A2 | Strong | Autosomal dominant | Bethlem myopathy 1A | 11 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| COL6A1 | Orphanet:610 | Bethlem muscular dystrophy |
| COL6A1 | Orphanet:646113 | Intermediate collagen VI-related muscular dystrophy |
| COL6A1 | Orphanet:75840 | Ullrich congenital muscular dystrophy |
| COL6A2 | Orphanet:289380 | Myosclerosis |
| COL6A2 | Orphanet:610 | Bethlem muscular dystrophy |
| COL6A2 | Orphanet:646113 | Intermediate collagen VI-related muscular dystrophy |
| COL6A2 | Orphanet:75840 | Ullrich congenital muscular dystrophy |
| COL6A3 | Orphanet:464440 | Primary dystonia, DYT27 type |
| COL6A3 | Orphanet:610 | Bethlem muscular dystrophy |
| COL6A3 | Orphanet:646113 | Intermediate collagen VI-related muscular dystrophy |
| COL6A3 | Orphanet:75840 | Ullrich congenital muscular dystrophy |
| SLC7A9 | Orphanet:93613 | Cystinuria type B |
| CLCN5 | Orphanet:93622 | Dent disease type 1 |
| COL12A1 | Orphanet:536516 | Myopathic Ehlers-Danlos syndrome |
| COL12A1 | Orphanet:610 | Bethlem muscular dystrophy |
| COL12A1 | Orphanet:75840 | Ullrich congenital muscular dystrophy |
| DMPK | Orphanet:589821 | Congenital-onset Steinert myotonic dystrophy |
| DMPK | Orphanet:589824 | Childhood-onset Steinert myotonic dystrophy |
| DMPK | Orphanet:589827 | Juvenile-onset Steinert myotonic dystrophy |
| DMPK | Orphanet:589830 | Adult-onset Steinert myotonic dystrophy |
| DMPK | Orphanet:589833 | Late-onset Steinert myotonic dystrophy |
| LMNA | Orphanet:154 | Familial isolated dilated cardiomyopathy |
| LMNA | Orphanet:157973 | Congenital muscular dystrophy due to LMNA mutation |
| LMNA | Orphanet:1662 | Restrictive dermopathy |
| LMNA | Orphanet:168796 | Heart-hand syndrome, Slovenian type |
| LMNA | Orphanet:2229 | Dilated cardiomyopathy-hypergonadotropic hypogonadism syndrome |
| LMNA | Orphanet:2348 | Familial partial lipodystrophy, Dunnigan type |
| LMNA | Orphanet:280365 | Autosomal semi-dominant severe lipodystrophic laminopathy |
| LMNA | Orphanet:293888 | Inherited isolated arrhythmogenic cardiomyopathy, dominant-left variant |
| LMNA | Orphanet:293899 | Inherited isolated arrhythmogenic ventricular dysplasia, biventricular variant |
| LMNA | Orphanet:293910 | Inherited isolated arrhythmogenic cardiomyopathy, dominant-right variant |
| LMNA | Orphanet:300751 | Familial dilated cardiomyopathy with conduction defect due to LMNA mutation |
| LMNA | Orphanet:363618 | LMNA-related cardiocutaneous progeria syndrome |
| LMNA | Orphanet:54260 | Left ventricular noncompaction |
| LMNA | Orphanet:675396 | Epithelioid hemangioma |
| LMNA | Orphanet:740 | Hutchinson-Gilford progeria syndrome |
| LMNA | Orphanet:79084 | Familial partial lipodystrophy, Köbberling type |
| LMNA | Orphanet:79474 | Atypical Werner syndrome |
| LMNA | Orphanet:90153 | Mandibuloacral dysplasia with type A lipodystrophy |
| LMNA | Orphanet:98853 | Autosomal dominant Emery-Dreifuss muscular dystrophy |
| LMNA | Orphanet:98855 | Autosomal recessive Emery-Dreifuss muscular dystrophy |
| LMNA | Orphanet:98856 | Charcot-Marie-Tooth disease type 2B1 |
Cohort genes → proteins
10 cohort genes, 10 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 10 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| COL6A1 | HGNC:2211 | ENSG00000142156 | P12109 | Collagen alpha-1(VI) chain | gencc,clinvar |
| COL6A2 | HGNC:2212 | ENSG00000142173 | P12110 | Collagen alpha-2(VI) chain | gencc,clinvar |
| COL6A3 | HGNC:2213 | ENSG00000163359 | P12111 | Collagen alpha-3(VI) chain | gencc,clinvar |
| SLC7A9 | HGNC:11067 | ENSG00000021488 | P82251 | b(0,+)-type amino acid transporter 1 | clinvar |
| CLCN5 | HGNC:2023 | ENSG00000171365 | P51795 | H(+)/Cl(-) exchange transporter 5 | clinvar |
| ANKMY1 | HGNC:20987 | ENSG00000144504 | Q9P2S6 | Ankyrin repeat and MYND domain-containing protein 1 | clinvar |
| COL12A1 | HGNC:2188 | ENSG00000111799 | Q99715 | Collagen alpha-1(XII) chain | clinvar |
| ACKR3 | HGNC:23692 | ENSG00000144476 | P25106 | Atypical chemokine receptor 3 | clinvar |
| DMPK | HGNC:2933 | ENSG00000104936 | Q09013 | Myotonin-protein kinase | clinvar |
| LMNA | HGNC:6636 | ENSG00000160789 | P02545 | Prelamin-A/C | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| COL6A1 | Collagen alpha-1(VI) chain | Collagen VI acts as a cell-binding protein. |
| COL6A2 | Collagen alpha-2(VI) chain | Collagen VI acts as a cell-binding protein. |
| COL6A3 | Collagen alpha-3(VI) chain | Collagen VI acts as a cell-binding protein. |
| SLC7A9 | b(0,+)-type amino acid transporter 1 | Associates with SLC3A1 to form a functional transporter complex that mediates the electrogenic exchange between cationic amino acids and neutral amino acids, with a stoichiometry of 1:1. |
| CLCN5 | H(+)/Cl(-) exchange transporter 5 | Proton-coupled chloride transporter. |
| COL12A1 | Collagen alpha-1(XII) chain | Type XII collagen interacts with type I collagen-containing fibrils, the COL1 domain could be associated with the surface of the fibrils, and the COL2 and NC3 domains may be localized in the perifibrillar matrix. |
| ACKR3 | Atypical chemokine receptor 3 | Atypical chemokine receptor that controls chemokine levels and localization via high-affinity chemokine binding that is uncoupled from classic ligand-driven signal transduction cascades, resulting instead in chemokine sequestration, degrad… |
| DMPK | Myotonin-protein kinase | Non-receptor serine/threonine protein kinase which is necessary for the maintenance of skeletal muscle structure and function. |
| LMNA | Prelamin-A/C | Lamins are intermediate filament proteins that assemble into a filamentous meshwork, and which constitute the major components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane. |
Protein-family classification
Druggable: 5 · Difficult: 1 · 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 |
|---|---|---|---|
| Antibody/Immunoglobulin | 2 | 5.8× | 0.264 |
| Transporter | 1 | 7.8× | 0.364 |
| Kinase | 1 | 2.8× | 0.521 |
| GPCR | 1 | 2.4× | 0.521 |
| Transcription factor | 1 | 0.8× | 0.870 |
| Other/Unknown | 4 | 0.7× | 0.907 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| COL6A1 | Other/Unknown | no | VWF_A, Collagen, vWFA_dom_sf | |
| COL6A2 | Other/Unknown | no | VWF_A, Collagen, vWFA_dom_sf | |
| COL6A3 | Antibody/Immunoglobulin | yes | VWF_A, Kunitz_BPTI, FN3_dom | |
| SLC7A9 | Transporter | yes | AA/rel_permease1, AminoAcid_Transporter | |
| CLCN5 | Other/Unknown | no | CBS_dom, ClC, Cl_channel-5 | |
| ANKMY1 | Transcription factor | no | Ankyrin_rpt, Znf_MYND, MORN | |
| COL12A1 | Antibody/Immunoglobulin | yes | VWF_A, FN3_dom, Collagen | |
| ACKR3 | GPCR | yes | GPCR_Rhodpsn, ACKR3, GPCR_Rhodpsn_7TM | |
| DMPK | Kinase | yes | 2.7.11.1 | Prot_kinase_dom, AGC-kinase_C, Ser/Thr_kinase_AS |
| LMNA | Other/Unknown | no | Lamin_tail_dom, IF_conserved, Lamin_tail_dom_sf |
Expression context
Cohort genes with no expression data: 0.
10 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) | 10 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| stromal cell of endometrium | 3 |
| tendon of biceps brachii | 2 |
| right coronary artery | 2 |
| secondary oocyte | 2 |
| mucosa of stomach | 2 |
| lower esophagus muscularis layer | 1 |
| descending thoracic aorta | 1 |
| skin of hip | 1 |
| visceral pleura | 1 |
| ileal mucosa | 1 |
| jejunal mucosa | 1 |
| corpus epididymis | 1 |
| renal medulla | 1 |
| left testis | 1 |
| right testis | 1 |
| right uterine tube | 1 |
| calcaneal tendon | 1 |
| cartilage tissue | 1 |
| tibia | 1 |
| synovial joint | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| COL6A1 | 291 | ubiquitous | marker | stromal cell of endometrium, tendon of biceps brachii, lower esophagus muscularis layer |
| COL6A2 | 263 | ubiquitous | marker | stromal cell of endometrium, right coronary artery, descending thoracic aorta |
| COL6A3 | 264 | broad | marker | stromal cell of endometrium, visceral pleura, skin of hip |
| SLC7A9 | 173 | tissue_specific | marker | ileal mucosa, secondary oocyte, jejunal mucosa |
| CLCN5 | 218 | ubiquitous | marker | renal medulla, secondary oocyte, corpus epididymis |
| ANKMY1 | 191 | ubiquitous | marker | right uterine tube, right testis, left testis |
| COL12A1 | 240 | ubiquitous | marker | tibia, calcaneal tendon, cartilage tissue |
| ACKR3 | 278 | ubiquitous | marker | synovial joint, vena cava, tendon of biceps brachii |
| DMPK | 246 | broad | marker | apex of heart, right coronary artery, mucosa of stomach |
| LMNA | 295 | ubiquitous | marker | nipple, mucosa of stomach, skin of abdomen |
Protein interactions among cohort
Intra-cohort edges: 5.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| LMNA | 7,173 |
| COL6A1 | 3,049 |
| COL6A2 | 2,786 |
| DMPK | 2,467 |
| COL6A3 | 2,267 |
| COL12A1 | 2,219 |
| CLCN5 | 1,345 |
| ACKR3 | 1,142 |
| SLC7A9 | 1,106 |
| ANKMY1 | 495 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| COL12A1 | COL6A1 | string_interaction |
| COL12A1 | COL6A3 | string_interaction |
| COL6A1 | COL6A2 | string_interaction |
| COL6A1 | COL6A3 | string_interaction |
| COL6A2 | COL6A3 | string_interaction |
Structural data
PDB: 9 · AlphaFold-only: 1 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| LMNA | P02545 | 28 |
| ACKR3 | P25106 | 14 |
| COL6A3 | P12111 | 6 |
| SLC7A9 | P82251 | 4 |
| CLCN5 | P51795 | 2 |
| DMPK | Q09013 | 2 |
| COL6A1 | P12109 | 1 |
| COL6A2 | P12110 | 1 |
| COL12A1 | Q99715 | 1 |
AlphaFold-only cohort genes (top 30 by pLDDT)
| Symbol | UniProt | pLDDT |
|---|---|---|
| ANKMY1 | Q9P2S6 | 78.09 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 44. Enrichment computed across 10 evidence-associated genes (9 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 9 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Collagen chain trimerization | 4 | 115.3× | 1e-06 | COL6A1, COL6A2, COL6A3, COL12A1 |
| Assembly of collagen fibrils and other multimeric structures | 4 | 89.0× | 1e-06 | COL6A1, COL6A2, COL6A3, COL12A1 |
| Collagen degradation | 4 | 78.1× | 1e-06 | COL6A1, COL6A2, COL6A3, COL12A1 |
| Collagen biosynthesis and modifying enzymes | 4 | 75.8× | 1e-06 | COL6A1, COL6A2, COL6A3, COL12A1 |
| Signaling by PDGF | 3 | 84.6× | 4e-05 | COL6A1, COL6A2, COL6A3 |
| NCAM1 interactions | 3 | 82.8× | 4e-05 | COL6A1, COL6A2, COL6A3 |
| ECM proteoglycans | 3 | 50.1× | 1e-04 | COL6A1, COL6A2, COL6A3 |
| Integrin cell surface interactions | 3 | 44.8× | 2e-04 | COL6A1, COL6A2, COL6A3 |
| Defective SLC3A1 causes cystinuria (CSNU) | 1 | 634.4× | 0.007 | SLC7A9 |
| Defective amino acid transport by SLC7A9 causes cystinuria (CSNU) | 1 | 634.4× | 0.007 | SLC7A9 |
| Breakdown of the nuclear lamina | 1 | 423.0× | 0.009 | LMNA |
| Depolymerization of the Nuclear Lamina | 1 | 84.6× | 0.043 | LMNA |
| Initiation of Nuclear Envelope (NE) Reformation | 1 | 66.8× | 0.050 | LMNA |
| IRE1alpha activates chaperones | 1 | 57.7× | 0.050 | LMNA |
| Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer’s disease models | 1 | 57.7× | 0.050 | LMNA |
| Nuclear Envelope Breakdown | 1 | 50.8× | 0.053 | LMNA |
| Basigin interactions | 1 | 48.8× | 0.053 | SLC7A9 |
| Unfolded Protein Response (UPR) | 1 | 39.6× | 0.061 | LMNA |
| Amino acid transport across the plasma membrane | 1 | 33.4× | 0.068 | SLC7A9 |
| Oncogenic MAPK signaling | 1 | 27.6× | 0.079 | LMNA |
| XBP1(S) activates chaperone genes | 1 | 23.9× | 0.083 | LMNA |
| Ion homeostasis | 1 | 22.7× | 0.083 | DMPK |
| SLC transporter disorders | 1 | 22.7× | 0.083 | SLC7A9 |
| Chemokine receptors bind chemokines | 1 | 20.8× | 0.086 | ACKR3 |
| Signaling by BRAF and RAF1 fusions | 1 | 18.9× | 0.091 | LMNA |
| Meiotic synapsis | 1 | 15.7× | 0.101 | LMNA |
| Disorders of transmembrane transporters | 1 | 15.5× | 0.101 | SLC7A9 |
| Stimuli-sensing channels | 1 | 15.1× | 0.101 | CLCN5 |
| R-HSA-425393 | 1 | 14.4× | 0.102 | SLC7A9 |
| Cell surface interactions at the vascular wall | 1 | 10.6× | 0.133 | SLC7A9 |
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 |
|---|---|---|---|---|
| muscle cell apoptotic process | 2 | 1872.4× | 3e-05 | COL6A1, DMPK |
| response to UV | 3 | 122.1× | 7e-05 | COL6A1, COL6A2, COL6A3 |
| cell adhesion | 5 | 20.8× | 7e-05 | COL6A1, COL6A2, COL6A3, COL12A1, ACKR3 |
| phosphatidylinositol 3-kinase/protein kinase B signal transduction | 3 | 70.2× | 3e-04 | COL6A1, COL6A2, COL6A3 |
| neuron apoptotic process | 3 | 61.7× | 3e-04 | COL6A1, COL6A2, COL6A3 |
| nuclear envelope organization | 2 | 220.3× | 7e-04 | DMPK, LMNA |
| endodermal cell differentiation | 2 | 110.1× | 0.003 | COL6A1, COL12A1 |
| regulation of excitatory postsynaptic membrane potential involved in skeletal muscle contraction | 1 | 1872.4× | 0.007 | DMPK |
| response to polyamine macromolecule | 1 | 1872.4× | 0.007 | COL6A1 |
| response to glucose | 2 | 56.7× | 0.007 | COL6A2, COL6A3 |
| collagen fibril organization | 2 | 49.9× | 0.008 | COL6A1, COL12A1 |
| regulation of skeletal muscle contraction by calcium ion signaling | 1 | 936.2× | 0.010 | DMPK |
| oculomotor nerve development | 1 | 936.2× | 0.010 | ACKR3 |
| response to decreased oxygen levels | 1 | 936.2× | 0.010 | COL6A1 |
| limb joint morphogenesis | 1 | 624.1× | 0.010 | COL6A1 |
| fat cell proliferation | 1 | 624.1× | 0.010 | COL6A1 |
| multicellular organismal locomotion | 1 | 624.1× | 0.010 | COL6A1 |
| regulation of collagen fibril organization | 1 | 624.1× | 0.010 | COL6A1 |
| DNA double-strand break attachment to nuclear envelope | 1 | 624.1× | 0.010 | LMNA |
| muscle organ development | 2 | 37.1× | 0.010 | COL6A3, LMNA |
| muscle system process | 1 | 468.1× | 0.011 | COL6A1 |
| establishment or maintenance of microtubule cytoskeleton polarity | 1 | 468.1× | 0.011 | LMNA |
| sensory perception of mechanical stimulus | 1 | 468.1× | 0.011 | COL6A1 |
| regulation of synapse structural plasticity | 1 | 468.1× | 0.011 | DMPK |
| positive regulation of mesenchymal stem cell migration | 1 | 468.1× | 0.011 | ACKR3 |
| regulation of myotube differentiation | 1 | 374.5× | 0.012 | DMPK |
| nuclear pore localization | 1 | 374.5× | 0.012 | LMNA |
| response to bleomycin | 1 | 374.5× | 0.012 | COL6A1 |
| L-cystine transport | 1 | 312.1× | 0.013 | SLC7A9 |
| apoptotic nuclear changes | 1 | 312.1× | 0.013 | COL6A1 |
Therapeutics
Drug target analysis
Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 8
Druggability breadth: 6 of 10 evidence-associated genes (60%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Genes with an approved drug
The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.
| Symbol | Example approved molecule |
|---|---|
| DMPK | FEDRATINIB |
| LMNA | BEPRIDIL |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| LMNA | 823 | 4 |
| DMPK | 20 | 4 |
| COL6A1 | 0 | 0 |
| COL6A2 | 0 | 0 |
| COL6A3 | 0 | 0 |
| SLC7A9 | 0 | 0 |
| CLCN5 | 0 | 0 |
| ANKMY1 | 0 | 0 |
| COL12A1 | 0 | 0 |
| ACKR3 | 0 | 0 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| FEDRATINIB | 4 | DMPK |
| RUXOLITINIB | 4 | DMPK |
| TOFACITINIB CITRATE | 4 | DMPK |
| TOFACITINIB | 4 | DMPK |
| BOSUTINIB | 4 | DMPK |
| DASATINIB | 4 | DMPK |
| ERLOTINIB | 4 | DMPK, LMNA |
| CRIZOTINIB | 4 | DMPK |
| MIDOSTAURIN | 4 | DMPK |
| GEFITINIB | 4 | DMPK |
| BEPRIDIL | 4 | LMNA |
| PHENYLBUTAZONE | 4 | LMNA |
| CEFOTAXIME SODIUM | 4 | LMNA |
| DIENESTROL | 4 | LMNA |
| IFOSFAMIDE | 4 | LMNA |
| PROGESTERONE | 4 | LMNA |
| CLOTRIMAZOLE | 4 | LMNA |
| DAPSONE | 4 | LMNA |
| AMINOCAPROIC ACID | 4 | LMNA |
| FLUCONAZOLE | 4 | LMNA |
| COLCHICINE | 4 | LMNA |
| NABUMETONE | 4 | LMNA |
| OXAPROZIN | 4 | LMNA |
| BUMETANIDE | 4 | LMNA |
| GLIPIZIDE | 4 | LMNA |
| BROMFENAC | 4 | LMNA |
| ROPIVACAINE | 4 | LMNA |
| TIZANIDINE | 4 | LMNA |
| METAXALONE | 4 | LMNA |
| CARBAMAZEPINE | 4 | LMNA |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 1.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| DMPK | 210 | Binding:210 |
| ACKR3 | 102 | Binding:77, Functional:24, ADMET:1 |
| LMNA | 12 | Binding:9, Functional:3 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| DMPK | 2.7.11.1 | non-specific serine/threonine protein kinase |
Cohort genes with high screening signal
≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.
| Symbol | ChEMBL assays |
|---|---|
| ACKR3 | 102 |
| DMPK | 210 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 10; with CPIC/DPWG dosing guidelines: 0.
No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).
Chemical tractability of cohort targets
30 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.
| Compound | Max phase | Cohort target (bioactivity) |
|---|---|---|
| FEDRATINIB | 4 | DMPK |
| RUXOLITINIB | 4 | DMPK |
| TOFACITINIB CITRATE | 4 | DMPK |
| TOFACITINIB | 4 | DMPK |
| BOSUTINIB | 4 | DMPK |
| DASATINIB | 4 | DMPK |
| ERLOTINIB | 4 | DMPK, LMNA |
| CRIZOTINIB | 4 | DMPK |
| MIDOSTAURIN | 4 | DMPK |
| GEFITINIB | 4 | DMPK |
| BEPRIDIL | 4 | LMNA |
| PHENYLBUTAZONE | 4 | LMNA |
| CEFOTAXIME SODIUM | 4 | LMNA |
| DIENESTROL | 4 | LMNA |
| IFOSFAMIDE | 4 | LMNA |
| PROGESTERONE | 4 | LMNA |
| CLOTRIMAZOLE | 4 | LMNA |
| DAPSONE | 4 | LMNA |
| AMINOCAPROIC ACID | 4 | LMNA |
| FLUCONAZOLE | 4 | LMNA |
| COLCHICINE | 4 | LMNA |
| NABUMETONE | 4 | LMNA |
| OXAPROZIN | 4 | LMNA |
| BUMETANIDE | 4 | LMNA |
| GLIPIZIDE | 4 | LMNA |
| BROMFENAC | 4 | LMNA |
| ROPIVACAINE | 4 | LMNA |
| TIZANIDINE | 4 | LMNA |
| METAXALONE | 4 | LMNA |
| CARBAMAZEPINE | 4 | LMNA |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 2 | DMPK, LMNA |
| B | Phased (≥1) drug, not yet approved | 0 | |
| C | Druggable family + PDB, no drug | 4 | COL6A3, SLC7A9, COL12A1, ACKR3 |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 4 | COL6A1, COL6A2, CLCN5, ANKMY1 |
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) |
|---|---|---|
| ACKR3 | 102 | — |
| COL6A1 | 0 | — |
| COL6A2 | 0 | — |
| COL6A3 | 0 | — |
| SLC7A9 | 0 | — |
| CLCN5 | 0 | — |
| ANKMY1 | 0 | — |
| COL12A1 | 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 |
|---|---|---|---|
| NCT04020159 | Not specified | UNKNOWN | Global Registry for COL6-related Dystrophies |