Bethlem myopathy 1B

Summary

Bethlem myopathy 1B (MONDO:0958233) is a disease with 2 cohort genes.

At a glance

• Cohort genes: 2
• ClinVar variants: 32

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Bethlem myopathy 1B
Mondo ID	MONDO:0958233
OMIM	620725
DOID	DOID:0061199
UMLS	C5935580
MedGen	1859128
GARD	0026980
Is cancer (heuristic)	no

Data availability: 32 ClinVar variants.

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 1B

Related subtypes (3): Bethlem myopathy 1A, Bethlem myopathy 2, 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

32 retrieved; paginated sample, class counts are floors:

8 conflicting classifications of pathogenicity, 8 pathogenic, 6 uncertain significance, 5 pathogenic/likely pathogenic, 5 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
283950	NM_001848.3(COL6A1):c.1611+1G>A	COL6A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1488541	NM_001849.4(COL6A2):c.2099G>A (p.Gly700Asp)	COL6A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
17155	NM_001849.4(COL6A2):c.811G>A (p.Gly271Ser)	COL6A2	Pathogenic	criteria provided, multiple submitters, no conflicts
17159	NM_001849.4(COL6A2):c.1861G>A (p.Asp621Asn)	COL6A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
17163	NM_001849.4(COL6A2):c.1000-2A>G	COL6A2	Pathogenic	criteria provided, single submitter
2444078	NM_001849.4(COL6A2):c.1382dup (p.Asn461fs)	COL6A2	Pathogenic	criteria provided, single submitter
265506	NM_001849.4(COL6A2):c.1970-9G>A	COL6A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2765800	NM_001849.4(COL6A2):c.1990C>T (p.Gln664Ter)	COL6A2	Pathogenic	criteria provided, multiple submitters, no conflicts
3256542	NM_001849.4(COL6A2):c.954+1G>A	COL6A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
379733	NM_001849.4(COL6A2):c.1572+1G>A	COL6A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
501184	NM_001849.4(COL6A2):c.900+1G>A	COL6A2	Pathogenic	criteria provided, multiple submitters, no conflicts
549682	NM_001849.4(COL6A2):c.1055delG	COL6A2	Pathogenic	criteria provided, single submitter
93907	NM_001849.4(COL6A2):c.1461del (p.Ser488fs)	COL6A2	Pathogenic	criteria provided, multiple submitters, no conflicts
3896819	NM_001849.4(COL6A2):c.595C>T (p.Gln199Ter)	COL6A2	Likely pathogenic	criteria provided, single submitter
3896821	NM_001849.4(COL6A2):c.901-2A>C	COL6A2	Likely pathogenic	criteria provided, single submitter
3896822	NM_001849.4(COL6A2):c.2065G>T (p.Glu689Ter)	COL6A2	Likely pathogenic	criteria provided, single submitter
3899380	NM_001849.4(COL6A2):c.1905G>T (p.Lys635Asn)	COL6A2	Likely pathogenic	criteria provided, single submitter
4279611	NM_001849.4(COL6A2):c.928-2_928-1del	COL6A2	Likely pathogenic	criteria provided, single submitter
1582979	NM_001849.4(COL6A2):c.2548C>T (p.His850Tyr)	COL6A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
166930	NM_001849.4(COL6A2):c.1162G>A (p.Gly388Arg)	COL6A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
17164	NM_001849.4(COL6A2):c.2795C>T (p.Pro932Leu)	COL6A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
210747	NM_001849.4(COL6A2):c.2489G>A (p.Arg830Gln)	COL6A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
285251	NM_001849.4(COL6A2):c.955-10C>T	COL6A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
287935	NM_001849.4(COL6A2):c.2809C>T (p.Arg937Trp)	COL6A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
476487	NM_001849.4(COL6A2):c.344G>A (p.Arg115Gln)	COL6A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
93927	NM_001849.4(COL6A2):c.1970-3C>A	COL6A2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1020091	NM_001849.4(COL6A2):c.709G>A (p.Val237Ile)	COL6A2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1899537	NM_001849.4(COL6A2):c.3029T>C (p.Phe1010Ser)	COL6A2	Uncertain significance	criteria provided, multiple submitters, no conflicts
3896818	NM_001849.4(COL6A2):c.1922T>G (p.Val641Gly)	COL6A2	Uncertain significance	criteria provided, single submitter
4293351	NM_001849.4(COL6A2):c.1001G>A (p.Gly334Asp)	COL6A2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 7 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

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

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
COL6A1	HGNC:2211	ENSG00000142156	P12109	Collagen alpha-1(VI) chain	clinvar
COL6A2	HGNC:2212	ENSG00000142173	P12110	Collagen alpha-2(VI) chain	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.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.0

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
Other/Unknown	2	1.8×	0.312

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

Expression context

Cohort genes with no expression data: 0.

2 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
stromal cell of endometrium	2
lower esophagus muscularis layer	1
tendon of biceps brachii	1
descending thoracic aorta	1
right coronary artery	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

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COL6A1	3,049
COL6A2	2,786

Intra-cohort edges

A	B	Sources
COL6A1	COL6A2	string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
COL6A1	P12109	1
COL6A2	P12110	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. Enrichment computed across 2 evidence-associated genes (2 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Collagen chain trimerization	2	259.6×	4e-05	COL6A1, COL6A2
Signaling by PDGF	2	253.8×	4e-05	COL6A1, COL6A2
NCAM1 interactions	2	248.3×	4e-05	COL6A1, COL6A2
Assembly of collagen fibrils and other multimeric structures	2	200.3×	5e-05	COL6A1, COL6A2
Collagen degradation	2	175.7×	5e-05	COL6A1, COL6A2
Collagen biosynthesis and modifying enzymes	2	170.4×	5e-05	COL6A1, COL6A2
ECM proteoglycans	2	150.3×	5e-05	COL6A1, COL6A2
Integrin cell surface interactions	2	134.3×	5e-05	COL6A1, COL6A2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
response to UV	2	366.4×	5e-04	COL6A1, COL6A2
phosphatidylinositol 3-kinase/protein kinase B signal transduction	2	210.7×	7e-04	COL6A1, COL6A2
neuron apoptotic process	2	185.2×	7e-04	COL6A1, COL6A2
response to polyamine macromolecule	1	8426.0×	0.002	COL6A1
muscle cell apoptotic process	1	4213.0×	0.003	COL6A1
response to decreased oxygen levels	1	4213.0×	0.003	COL6A1
limb joint morphogenesis	1	2808.7×	0.003	COL6A1
fat cell proliferation	1	2808.7×	0.003	COL6A1
multicellular organismal locomotion	1	2808.7×	0.003	COL6A1
regulation of collagen fibril organization	1	2808.7×	0.003	COL6A1
muscle system process	1	2106.5×	0.003	COL6A1
sensory perception of mechanical stimulus	1	2106.5×	0.003	COL6A1
response to bleomycin	1	1685.2×	0.003	COL6A1
apoptotic nuclear changes	1	1404.3×	0.003	COL6A1
skeletal muscle tissue growth	1	1404.3×	0.003	COL6A1
cell adhesion	2	37.5×	0.003	COL6A1, COL6A2
mitochondrial depolarization	1	1203.7×	0.004	COL6A1
caveola assembly	1	1053.2×	0.004	COL6A1
lung epithelial cell differentiation	1	936.2×	0.004	COL6A1
reduction of food intake in response to dietary excess	1	842.6×	0.004	COL6A1
skeletal muscle fiber differentiation	1	842.6×	0.004	COL6A1
mitochondrial transmembrane transport	1	842.6×	0.004	COL6A1
tissue remodeling	1	648.1×	0.005	COL6A1
response to peptide	1	561.7×	0.005	COL6A1
response to reactive oxygen species	1	526.6×	0.005	COL6A1
energy reserve metabolic process	1	526.6×	0.005	COL6A1
collagen metabolic process	1	526.6×	0.005	COL6A1
lung morphogenesis	1	526.6×	0.005	COL6A1
respiratory system process	1	468.1×	0.005	COL6A1
2-oxoglutarate metabolic process	1	468.1×	0.005	COL6A1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 2 of 2 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
COL6A1	0	0
COL6A2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	COL6A1, COL6A2

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
COL6A1	0	—
COL6A2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.