Collagen 6-related myopathy

Summary

Collagen 6-related myopathy (MONDO:0100225) is a disease with 3 cohort genes. The dominant Reactome pathway is Collagen chain trimerization (3 cohort genes).

At a glance

• Cohort genes: 3
• ClinVar variants: 741

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	collagen 6-related myopathy
Mondo ID	MONDO:0100225
GARD	0012705
Is cancer (heuristic)	no

Also known as: collagen 6-related myopathy · collagen VI-related dystrophy · collagen VI-related muscle disorder · collagen VI-related muscular dystrophy · collagen VI-related myopathy

Data availability: 741 ClinVar variants.

Disease family

An umbrella term covering 3 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › muscle tissue disorder › skeletal muscle disorder › myopathy › collagen 6-related myopathy

Related subtypes (31): polyglucosan body myopathy, muscular atrophy, myopathy of extraocular muscle, acute quadriplegic myopathy, myofascial pain syndrome, myopathy with abnormal lipid metabolism, proximal myopathy with focal depletion of mitochondria, Brody myopathy, rippling muscle disease, myopathy due to myoadenylate deaminase deficiency, proximal myopathy with extrapyramidal signs, intermediate nemaline myopathy, hereditary inclusion-body myopathy, hereditary continuous muscle fiber activity, congenital myopathy, muscular dystrophy, metabolic myopathy, myositis disease, myopathy caused by variation in CRPPA, drug-induced myopathy, myopathy caused by variation in FKRP, myopathy caused by variation in FKTN, myopathy caused by variation in POMGNT1, myopathy caused by variation in POMGNT2, myopathy caused by variation in POMT1, myopathy caused by variation in POMT2, myopathy caused by variation in GMPPB, FHL1-related myopathy, myopathy, sarcoplasmic body, myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis 2, myopathy with myalgia, increased serum creatine kinase, and with or without episodic rhabdomyolysis

Subtypes (3): Ullrich congenital muscular dystrophy 1A, myosclerosis, Bethlem myopathy 1A

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:

317 conflicting classifications of pathogenicity, 120 uncertain significance, 86 benign/likely benign, 42 benign, 23 likely benign, 10 pathogenic/likely pathogenic, 2 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1328167	NM_001848.3(COL6A1):c.824G>A (p.Gly275Glu)	COL6A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
17180	NM_001848.3(COL6A1):c.850G>A (p.Gly284Arg)	COL6A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
570612	NM_001848.3(COL6A1):c.788G>T (p.Gly263Val)	COL6A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
265506	NM_001849.4(COL6A2):c.1970-9G>A	COL6A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
29644	NM_001849.4(COL6A2):c.2611G>A (p.Asp871Asn)	COL6A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
476449	NM_001849.4(COL6A2):c.115+2T>C	COL6A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
476471	NM_001849.4(COL6A2):c.2572C>T (p.Gln858Ter)	COL6A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
498571	NM_001849.4(COL6A2):c.1053+1G>C	COL6A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1707195	NM_004369.4(COL6A3):c.6282+1G>C	COL6A3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
286745	NM_004369.4(COL6A3):c.761del (p.Gly254fs)	COL6A3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
493328	NM_001849.4(COL6A2):c.2627G>A (p.Arg876His)	COL6A2	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3062066	NM_004369.4(COL6A3):c.6156G>A (p.Lys2052=)	COL6A3	Likely pathogenic	criteria provided, single submitter
1055222	NM_001848.3(COL6A1):c.1960G>C (p.Glu654Gln)	COL6A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
128813	NM_001848.3(COL6A1):c.349G>A (p.Val117Met)	COL6A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1391450	NM_001848.3(COL6A1):c.181A>G (p.Lys61Glu)	COL6A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
162529	NM_001848.3(COL6A1):c.2635A>G (p.Ser879Gly)	COL6A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
195150	NM_001848.3(COL6A1):c.202C>T (p.Arg68Cys)	COL6A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
195151	NM_001848.3(COL6A1):c.170C>A (p.Ala57Asp)	COL6A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
196680	NM_001848.3(COL6A1):c.2045G>A (p.Arg682Gln)	COL6A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
196948	NM_001848.3(COL6A1):c.2821C>T (p.Leu941Phe)	COL6A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
196954	NM_001848.3(COL6A1):c.2809A>G (p.Lys937Glu)	COL6A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
258287	NM_001848.3(COL6A1):c.1584G>A (p.Pro528=)	COL6A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
258290	NM_001848.3(COL6A1):c.1671C>T (p.Asp557=)	COL6A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
281119	NM_001848.3(COL6A1):c.1298G>A (p.Arg433Gln)	COL6A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
281309	NM_001848.3(COL6A1):c.1555G>A (p.Glu519Lys)	COL6A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
281741	NM_001848.3(COL6A1):c.1399-3C>T	COL6A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
281842	NM_001848.3(COL6A1):c.2637C>T (p.Ser879=)	COL6A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
282529	NM_001848.3(COL6A1):c.1254C>T (p.Asp418=)	COL6A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
282894	NM_001848.3(COL6A1):c.1115A>G (p.Glu372Gly)	COL6A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
283014	NM_001848.3(COL6A1):c.2595G>A (p.Thr865=)	COL6A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 11 · 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
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

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

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
COL6A3	HGNC:2213	ENSG00000163359	P12111	Collagen alpha-3(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.
COL6A3	Collagen alpha-3(VI) chain	Collagen VI acts as a cell-binding protein.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.33

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	1	9.7×	0.199
Other/Unknown	2	1.2×	0.587

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

Expression context

Cohort genes with no expression data: 0.

3 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
stromal cell of endometrium	3
lower esophagus muscularis layer	1
tendon of biceps brachii	1
descending thoracic aorta	1
right coronary artery	1
skin of hip	1
visceral pleura	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

Protein interactions among cohort

Intra-cohort edges: 3.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COL6A1	3,049
COL6A2	2,786
COL6A3	2,267

Intra-cohort edges

A	B	Sources
COL6A1	COL6A2	string_interaction
COL6A1	COL6A3	string_interaction
COL6A2	COL6A3	string_interaction

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
COL6A3	P12111	6
COL6A1	P12109	1
COL6A2	P12110	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. Enrichment computed across 3 evidence-associated genes (3 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 3 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	3	259.6×	2e-07	COL6A1, COL6A2, COL6A3
Signaling by PDGF	3	253.8×	2e-07	COL6A1, COL6A2, COL6A3
NCAM1 interactions	3	248.3×	2e-07	COL6A1, COL6A2, COL6A3
Assembly of collagen fibrils and other multimeric structures	3	200.3×	2e-07	COL6A1, COL6A2, COL6A3
Collagen degradation	3	175.7×	3e-07	COL6A1, COL6A2, COL6A3
Collagen biosynthesis and modifying enzymes	3	170.4×	3e-07	COL6A1, COL6A2, COL6A3
ECM proteoglycans	3	150.3×	3e-07	COL6A1, COL6A2, COL6A3
Integrin cell surface interactions	3	134.3×	4e-07	COL6A1, COL6A2, COL6A3

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 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	3	366.4×	1e-06	COL6A1, COL6A2, COL6A3
phosphatidylinositol 3-kinase/protein kinase B signal transduction	3	210.7×	4e-06	COL6A1, COL6A2, COL6A3
neuron apoptotic process	3	185.2×	4e-06	COL6A1, COL6A2, COL6A3
cell adhesion	3	37.5×	3e-04	COL6A1, COL6A2, COL6A3
response to glucose	2	170.2×	7e-04	COL6A2, COL6A3
response to polyamine macromolecule	1	5617.3×	0.002	COL6A1
muscle cell apoptotic process	1	2808.7×	0.003	COL6A1
response to decreased oxygen levels	1	2808.7×	0.003	COL6A1
limb joint morphogenesis	1	1872.4×	0.003	COL6A1
fat cell proliferation	1	1872.4×	0.003	COL6A1
multicellular organismal locomotion	1	1872.4×	0.003	COL6A1
regulation of collagen fibril organization	1	1872.4×	0.003	COL6A1
muscle system process	1	1404.3×	0.004	COL6A1
sensory perception of mechanical stimulus	1	1404.3×	0.004	COL6A1
response to bleomycin	1	1123.5×	0.004	COL6A1
apoptotic nuclear changes	1	936.2×	0.005	COL6A1
skeletal muscle tissue growth	1	936.2×	0.005	COL6A1
mitochondrial depolarization	1	802.5×	0.005	COL6A1
caveola assembly	1	702.2×	0.005	COL6A1
lung epithelial cell differentiation	1	624.1×	0.006	COL6A1
reduction of food intake in response to dietary excess	1	561.7×	0.006	COL6A1
skeletal muscle fiber differentiation	1	561.7×	0.006	COL6A1
mitochondrial transmembrane transport	1	561.7×	0.006	COL6A1
tissue remodeling	1	432.1×	0.007	COL6A1
response to peptide	1	374.5×	0.007	COL6A1
response to reactive oxygen species	1	351.1×	0.007	COL6A1
energy reserve metabolic process	1	351.1×	0.007	COL6A1
collagen metabolic process	1	351.1×	0.007	COL6A1
lung morphogenesis	1	351.1×	0.007	COL6A1
respiratory system process	1	312.1×	0.007	COL6A1

Therapeutics

Drug target analysis

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

Druggability breadth: 3 of 3 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
COL6A3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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	1	COL6A3
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	COL6A1, COL6A2

Undrugged target profiles

3 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	—
COL6A3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.