Ullrich congenital muscular dystrophy 1A

Summary

Ullrich congenital muscular dystrophy 1A (MONDO:0009681) is a disease caused by variants in COL6A1, COL6A2, and COL6A3, with 5 cohort genes. The dominant Reactome pathway is Collagen chain trimerization (4 cohort genes).

At a glance

• Causal genes: COL6A1 (GenCC Strong), COL6A2 (GenCC Strong), COL6A3 (GenCC Strong)
• Cohort genes: 5
• ClinVar variants: 253

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Ullrich congenital muscular dystrophy 1A
Mondo ID	MONDO:0009681
OMIM	254090
DOID	DOID:0060946
UMLS	C0410179
MedGen	98046
GARD	0024685
Is cancer (heuristic)	no

Also known as: UCMD1 · Ullrich congenital muscular dystrophy 1 · Ullrich congenital muscular dystrophy type 1

Data availability: 253 ClinVar variants · 13 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › congenital muscular dystrophy › Ullrich congenital muscular dystrophy › Ullrich congenital muscular dystrophy 1A

Related subtypes (3): Ullrich congenital muscular dystrophy 2, Ullrich congenital muscular dystrophy 1B, Ullrich congenital muscular dystrophy 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

253 retrieved; paginated sample, class counts are floors:

69 conflicting classifications of pathogenicity, 46 uncertain significance, 36 benign, 31 pathogenic, 25 likely pathogenic, 23 pathogenic/likely pathogenic, 19 benign/likely benign, 4 likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1299552	NM_001848.3(COL6A1):c.2460C>A (p.Cys820Ter)	COL6A1	Pathogenic	criteria provided, single submitter
17176	NM_001848.3(COL6A1):c.428+1G>A	COL6A1	Pathogenic	criteria provided, multiple submitters, no conflicts
17177	NM_001848.3(COL6A1):c.857del (p.Pro286fs)	COL6A1	Pathogenic	no assertion criteria provided
17178	NM_001848.3(COL6A1):c.1465del (p.Ala489fs)	COL6A1	Pathogenic	no assertion criteria provided
17179	NM_001848.3(COL6A1):c.1977C>G (p.Tyr659Ter)	COL6A1	Pathogenic	no assertion criteria provided
17180	NM_001848.3(COL6A1):c.850G>A (p.Gly284Arg)	COL6A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
17182	NM_001848.3(COL6A1):c.841G>A (p.Gly281Arg)	COL6A1	Pathogenic	criteria provided, multiple submitters, no conflicts
2444174	NM_001848.3(COL6A1):c.234C>A (p.Tyr78Ter)	COL6A1	Pathogenic	criteria provided, single submitter
280099	NM_001848.3(COL6A1):c.842G>A (p.Gly281Glu)	COL6A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
285482	NM_001848.3(COL6A1):c.928_930del (p.Lys310del)	COL6A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
290695	NM_001848.3(COL6A1):c.957+1G>A	COL6A1	Pathogenic	criteria provided, multiple submitters, no conflicts
3383040	NM_001848.3(COL6A1):c.1006del	COL6A1	Pathogenic	criteria provided, single submitter
4291973	NM_001848.3(COL6A1):c.1496dup (p.Gly500fs)	COL6A1	Pathogenic	criteria provided, single submitter
4292581	NM_001848.3(COL6A1):c.2202_2203del (p.Gln735fs)	COL6A1	Pathogenic	criteria provided, single submitter
542998	NM_001848.3(COL6A1):c.930+189C>T	COL6A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
595434	NM_001848.3(COL6A1):c.1641_1642del (p.Asp548fs)	COL6A1	Pathogenic	criteria provided, multiple submitters, no conflicts
635019	NM_001848.3(COL6A1):c.904-39A>G	COL6A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
657156	NM_001848.3(COL6A1):c.887G>T (p.Gly296Val)	COL6A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
861529	NM_001848.3(COL6A1):c.554_555del (p.Lys185fs)	COL6A1	Pathogenic	criteria provided, multiple submitters, no conflicts
93894	NM_001848.3(COL6A1):c.868G>A (p.Gly290Arg)	COL6A1	Pathogenic	criteria provided, multiple submitters, no conflicts
93895	NM_001848.3(COL6A1):c.877G>A (p.Gly293Arg)	COL6A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
971352	NM_001848.3(COL6A1):c.805-2A>C	COL6A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1029383	NM_058174.3(COL6A2):c.2554C>T (p.Gln852Ter)	COL6A2	Pathogenic	criteria provided, single submitter
1691316	NM_001849.4(COL6A2):c.955-2A>C	COL6A2	Pathogenic	criteria provided, single submitter
1694468	NM_001849.4(COL6A2):c.101_104del (p.Asn34fs)	COL6A2	Pathogenic	criteria provided, single submitter
17167	NM_001849.4(COL6A2):c.847G>A (p.Gly283Arg)	COL6A2	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
280693	NM_001849.4(COL6A2):c.2422+1G>A	COL6A2	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
3367032	NM_001849.4(COL6A2):c.900+2T>G	COL6A2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 35 · Orphanet: 14 · 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
COL6A2	Definitive	Autosomal dominant	Ullrich congenital muscular dystrophy 1B	11
COL6A3	Definitive	Autosomal recessive	Ullrich congenital muscular dystrophy 1C	15
COL6A1	Strong	Autosomal dominant	Ullrich congenital muscular dystrophy 1A	9

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
COL12A1	Orphanet:536516	Myopathic Ehlers-Danlos syndrome
COL12A1	Orphanet:610	Bethlem muscular dystrophy
COL12A1	Orphanet:75840	Ullrich congenital muscular dystrophy

Cohort genes → proteins

5 cohort genes, 5 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	5

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
ELMO3	HGNC:17289	ENSG00000102890	Q96BJ8	Engulfment and cell motility protein 3	clinvar
COL12A1	HGNC:2188	ENSG00000111799	Q99715	Collagen alpha-1(XII) 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.
ELMO3	Engulfment and cell motility protein 3	Involved in cytoskeletal rearrangements required for phagocytosis of apoptotic cells and cell motility.
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.

Protein-family classification

Druggable: 2 · Difficult: 1 · Unknown: 2 · Druggable fraction: 0.4

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	11.7×	0.033
Scaffold/PPI	1	3.5×	0.386
Other/Unknown	2	0.7×	0.877

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
ELMO3	Scaffold/PPI	no		PH_domain, ELMO_dom, ARM-like
COL12A1	Antibody/Immunoglobulin	yes		VWF_A, FN3_dom, Collagen

Expression context

Cohort genes with no expression data: 0.

5 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)	5
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
body of pancreas	1
lower esophagus mucosa	1
mucosa of transverse colon	1
calcaneal tendon	1
cartilage tissue	1
tibia	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
ELMO3	203	broad	marker	mucosa of transverse colon, body of pancreas, lower esophagus mucosa
COL12A1	240	ubiquitous	marker	tibia, calcaneal tendon, cartilage tissue

Protein interactions among cohort

Intra-cohort edges: 5.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COL6A1	3,049
COL6A2	2,786
COL6A3	2,267
COL12A1	2,219
ELMO3	766

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
COL6A3	P12111	6
COL6A1	P12109	1
COL6A2	P12110	1
COL12A1	Q99715	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
ELMO3	Q96BJ8	89.04

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. Enrichment computed across 5 evidence-associated genes (4 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 4 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	259.6×	2e-09	COL6A1, COL6A2, COL6A3, COL12A1
Assembly of collagen fibrils and other multimeric structures	4	200.3×	2e-09	COL6A1, COL6A2, COL6A3, COL12A1
Collagen degradation	4	175.7×	2e-09	COL6A1, COL6A2, COL6A3, COL12A1
Collagen biosynthesis and modifying enzymes	4	170.4×	2e-09	COL6A1, COL6A2, COL6A3, COL12A1
Signaling by PDGF	3	190.3×	3e-07	COL6A1, COL6A2, COL6A3
NCAM1 interactions	3	186.2×	3e-07	COL6A1, COL6A2, COL6A3
ECM proteoglycans	3	112.7×	1e-06	COL6A1, COL6A2, COL6A3
Integrin cell surface interactions	3	100.8×	2e-06	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 5 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	219.8×	1e-05	COL6A1, COL6A2, COL6A3
phosphatidylinositol 3-kinase/protein kinase B signal transduction	3	126.4×	4e-05	COL6A1, COL6A2, COL6A3
neuron apoptotic process	3	111.1×	4e-05	COL6A1, COL6A2, COL6A3
cell adhesion	4	30.0×	5e-05	COL6A1, COL6A2, COL6A3, COL12A1
endodermal cell differentiation	2	198.3×	6e-04	COL6A1, COL12A1
response to glucose	2	102.1×	0.002	COL6A2, COL6A3
collagen fibril organization	2	89.9×	0.002	COL6A1, COL12A1
response to polyamine macromolecule	1	3370.4×	0.003	COL6A1
muscle cell apoptotic process	1	1685.2×	0.005	COL6A1
response to decreased oxygen levels	1	1685.2×	0.005	COL6A1
limb joint morphogenesis	1	1123.5×	0.005	COL6A1
fat cell proliferation	1	1123.5×	0.005	COL6A1
multicellular organismal locomotion	1	1123.5×	0.005	COL6A1
regulation of collagen fibril organization	1	1123.5×	0.005	COL6A1
muscle system process	1	842.6×	0.006	COL6A1
sensory perception of mechanical stimulus	1	842.6×	0.006	COL6A1
response to bleomycin	1	674.1×	0.007	COL6A1
apoptotic nuclear changes	1	561.7×	0.007	COL6A1
skeletal muscle tissue growth	1	561.7×	0.007	COL6A1
mitochondrial depolarization	1	481.5×	0.008	COL6A1
caveola assembly	1	421.3×	0.009	COL6A1
lung epithelial cell differentiation	1	374.5×	0.009	COL6A1
reduction of food intake in response to dietary excess	1	337.0×	0.009	COL6A1
skeletal muscle fiber differentiation	1	337.0×	0.009	COL6A1
mitochondrial transmembrane transport	1	337.0×	0.009	COL6A1
tissue remodeling	1	259.3×	0.011	COL6A1
response to peptide	1	224.7×	0.012	COL6A1
response to reactive oxygen species	1	210.7×	0.012	COL6A1
energy reserve metabolic process	1	210.7×	0.012	COL6A1
collagen metabolic process	1	210.7×	0.012	COL6A1

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 5

Druggability breadth: 3 of 5 evidence-associated genes (60%) 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
ELMO3	0	0
COL12A1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 5; 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	2	COL6A3, COL12A1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	3	COL6A1, COL6A2, ELMO3

Undrugged target profiles

5 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	—
ELMO3	0	—
COL12A1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.