Bethlem myopathy 1C

Summary

Bethlem myopathy 1C (MONDO:0958234) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 32

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Bethlem myopathy 1C
Mondo ID	MONDO:0958234
OMIM	620726
DOID	DOID:0061200
UMLS	C5935581
MedGen	1854240
GARD	0026981
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 1C

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

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:

13 uncertain significance, 7 pathogenic, 7 conflicting classifications of pathogenicity, 3 pathogenic/likely pathogenic, 1 likely pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
17149	NM_004369.4(COL6A3):c.5036G>A (p.Gly1679Glu)	COL6A3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
17153	NM_004369.4(COL6A3):c.6156+1_6156+2delinsTC	COL6A3	Pathogenic	no assertion criteria provided
17154	NM_004369.4(COL6A3):c.5177T>G (p.Leu1726Arg)	COL6A3	Pathogenic	no assertion criteria provided
196977	NM_004369.4(COL6A3):c.7447A>G (p.Lys2483Glu)	COL6A3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2745670	NM_004369.4(COL6A3):c.7094del	COL6A3	Pathogenic	criteria provided, multiple submitters, no conflicts
3050998	NM_004369.4(COL6A3):c.4789C>T (p.Arg1597Ter)	COL6A3	Pathogenic	criteria provided, single submitter
3252111	NM_004369.4(COL6A3):c.8540del (p.Asn2847fs)	COL6A3	Pathogenic	no assertion criteria provided
4087707	NM_004369.4(COL6A3):c.7253T>A (p.Phe2418Tyr)	COL6A3	Pathogenic	criteria provided, single submitter
419449	NM_004369.4(COL6A3):c.2506C>T (p.Arg836Ter)	COL6A3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
94956	NM_004369.4(COL6A3):c.6210+1G>A	COL6A3	Pathogenic	criteria provided, multiple submitters, no conflicts
4081277	NM_004369.4(COL6A3):c.3071-2A>G	COL6A3	Likely pathogenic	criteria provided, multiple submitters, no conflicts
224687	NM_004369.4(COL6A3):c.2218C>T (p.Arg740Cys)	COL6A3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
284121	NM_004369.4(COL6A3):c.3199G>A (p.Val1067Met)	COL6A3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
288613	NM_004369.4(COL6A3):c.9116C>T (p.Thr3039Met)	COL6A3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
288643	NM_004369.4(COL6A3):c.2231C>T (p.Pro744Leu)	COL6A3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
335132	NM_004369.4(COL6A3):c.3190C>T (p.Arg1064Trp)	COL6A3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
335144	NM_004369.4(COL6A3):c.466G>T (p.Asp156Tyr)	COL6A3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
3391076	NM_004369.4(COL6A3):c.3488T>C (p.Ile1163Thr)	COL6A3	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
2079058	NM_004369.4(COL6A3):c.1483C>A (p.Pro495Thr)	COL6A3	Uncertain significance	criteria provided, multiple submitters, no conflicts
284126	NM_004369.4(COL6A3):c.8966-3C>A	COL6A3	Uncertain significance	criteria provided, multiple submitters, no conflicts
284557	NM_004369.4(COL6A3):c.7375C>T (p.Arg2459Trp)	COL6A3	Uncertain significance	criteria provided, multiple submitters, no conflicts
3064829	NM_004369.4(COL6A3):c.5815C>G (p.Gln1939Glu)	COL6A3	Uncertain significance	criteria provided, single submitter
3065642	NM_004369.4(COL6A3):c.8056G>T (p.Glu2686Ter)	COL6A3	Uncertain significance	criteria provided, single submitter
3068257	NM_004369.4(COL6A3):c.3281C>T (p.Ala1094Val)	COL6A3	Uncertain significance	criteria provided, single submitter
3586194	NM_004369.4(COL6A3):c.1992C>T (p.Asn664=)	COL6A3	Uncertain significance	criteria provided, single submitter
4277938	NM_004369.4(COL6A3):c.6922G>T (p.Gly2308Cys)	COL6A3	Uncertain significance	criteria provided, single submitter
429218	NM_004369.4(COL6A3):c.8634_8651del (p.2875KPVTTT[1])	COL6A3	Uncertain significance	criteria provided, multiple submitters, no conflicts
523040	NM_004369.4(COL6A3):c.6520G>A (p.Gly2174Ser)	COL6A3	Uncertain significance	criteria provided, multiple submitters, no conflicts
949995	NM_004369.4(COL6A3):c.709+4A>G	COL6A3	Uncertain significance	criteria provided, multiple submitters, no conflicts
962811	NM_004369.4(COL6A3):c.7546A>G (p.Ser2516Gly)	COL6A3	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 4 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
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

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
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)
COL6A3	Collagen alpha-3(VI) chain	Collagen VI acts as a cell-binding protein.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Antibody/Immunoglobulin	1	29.2×	0.034

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
COL6A3	Antibody/Immunoglobulin	yes		VWF_A, Kunitz_BPTI, FN3_dom

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
skin of hip	1
stromal cell of endometrium	1
visceral pleura	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COL6A3	264	broad	marker	stromal cell of endometrium, visceral pleura, skin of hip

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COL6A3	2,267

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
COL6A3	P12111	6

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. Enrichment computed across 1 evidence-associated genes (1 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 1 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	1	259.6×	0.007	COL6A3
Signaling by PDGF	1	253.8×	0.007	COL6A3
NCAM1 interactions	1	248.3×	0.007	COL6A3
Assembly of collagen fibrils and other multimeric structures	1	200.3×	0.007	COL6A3
Collagen degradation	1	175.7×	0.007	COL6A3
Collagen biosynthesis and modifying enzymes	1	170.4×	0.007	COL6A3
ECM proteoglycans	1	150.3×	0.007	COL6A3
Integrin cell surface interactions	1	134.3×	0.007	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 1 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	1	366.4×	0.007	COL6A3
response to glucose	1	255.3×	0.007	COL6A3
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1	210.7×	0.007	COL6A3
neuron apoptotic process	1	185.2×	0.007	COL6A3
muscle organ development	1	166.8×	0.007	COL6A3
cell adhesion	1	37.5×	0.027	COL6A3

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 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
COL6A3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; 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	0

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
COL6A3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.