Ullrich congenital muscular dystrophy 2

Summary

Ullrich congenital muscular dystrophy 2 (MONDO:0014654) is a disease caused by COL12A1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: COL12A1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 3,417

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Ullrich congenital muscular dystrophy 2
Mondo ID	MONDO:0014654
OMIM	616470
DOID	DOID:0060948
UMLS	C4225314
MedGen	899150
GARD	0016120
Is cancer (heuristic)	no

Also known as: COL12A1 Ullrich congenital muscular dystrophy · UCMD2 · Ullrich congenital muscular dystrophy 2 · Ullrich congenital muscular dystrophy caused by mutation in COL12A1 · Ullrich congenital muscular dystrophy type 2

Data availability: 3,417 ClinVar variants · 1 GenCC gene-disease record.

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 2

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

600 retrieved; paginated sample, class counts are floors:

326 uncertain significance, 170 likely benign, 76 conflicting classifications of pathogenicity, 8 benign, 8 pathogenic, 7 benign/likely benign, 3 likely pathogenic, 2 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1062642	NM_004370.6(COL12A1):c.8100+3_8100+6del	COL12A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1069771	NM_004370.6(COL12A1):c.8571del (p.Pro2858fs)	COL12A1	Pathogenic	criteria provided, single submitter
1070407	NM_004370.6(COL12A1):c.7085del (p.Gln2362fs)	COL12A1	Pathogenic	criteria provided, single submitter
1073075	NC_000006.11:g.(?75796253)(75912518_?)del	COL12A1	Pathogenic	criteria provided, single submitter
1215037	NM_004370.6(COL12A1):c.5794+2T>A	COL12A1	Pathogenic	criteria provided, multiple submitters, no conflicts
1395130	NM_004370.6(COL12A1):c.27_42del (p.Ala10fs)	COL12A1	Pathogenic	criteria provided, single submitter
1444852	NM_004370.6(COL12A1):c.6737_6812del (p.Gln2246fs)	COL12A1	Pathogenic	criteria provided, single submitter
1453491	NM_004370.6(COL12A1):c.6819del (p.Phe2273fs)	COL12A1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1455959	NC_000006.11:g.(?75855798)(75861023_?)del	COL12A1	Pathogenic	criteria provided, single submitter
1459613	NC_000006.11:g.(?75833026)(75912508_?)del	COL12A1	Pathogenic	criteria provided, single submitter
1066887	NM_004370.6(COL12A1):c.6872-2A>G	COL12A1	Likely pathogenic	criteria provided, single submitter
1467502	NM_004370.6(COL12A1):c.8265+1G>A	COL12A1	Likely pathogenic	criteria provided, single submitter
1473846	NM_004370.6(COL12A1):c.8393_8415+5del	COL12A1	Likely pathogenic	criteria provided, single submitter
1001973	NM_004370.6(COL12A1):c.8857G>T (p.Ala2953Ser)	COL12A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1002779	NM_004370.6(COL12A1):c.5614C>T (p.Arg1872Cys)	COL12A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1009475	NM_004370.6(COL12A1):c.74-15CT[3]	COL12A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1020289	NM_004370.6(COL12A1):c.569C>A (p.Thr190Asn)	COL12A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1022101	NM_004370.6(COL12A1):c.1772C>G (p.Pro591Arg)	COL12A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1026861	NM_004370.6(COL12A1):c.4650C>G (p.His1550Gln)	COL12A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1036247	NM_004370.6(COL12A1):c.3952G>A (p.Ala1318Thr)	COL12A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1040854	NM_004370.6(COL12A1):c.6427G>C (p.Val2143Leu)	COL12A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1043877	NM_004370.6(COL12A1):c.7432C>T (p.Arg2478Trp)	COL12A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1044820	NM_004370.6(COL12A1):c.6549T>A (p.Asn2183Lys)	COL12A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1045236	NM_004370.6(COL12A1):c.5996T>G (p.Leu1999Arg)	COL12A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1047680	NM_004370.6(COL12A1):c.4781G>A (p.Arg1594His)	COL12A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1049088	NM_004370.6(COL12A1):c.1574A>T (p.Tyr525Phe)	COL12A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1051021	NM_004370.6(COL12A1):c.7331C>T (p.Ala2444Val)	COL12A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1053272	NM_004370.6(COL12A1):c.3714T>C (p.Ile1238=)	COL12A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1053823	NM_004370.6(COL12A1):c.5510G>A (p.Gly1837Glu)	COL12A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1054455	NM_004370.6(COL12A1):c.5673C>G (p.Ile1891Met)	COL12A1	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 3 · 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
COL12A1	Strong	Autosomal recessive	Ullrich congenital muscular dystrophy 2	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COL12A1	Orphanet:536516	Myopathic Ehlers-Danlos syndrome
COL12A1	Orphanet:610	Bethlem muscular dystrophy
COL12A1	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
COL12A1	HGNC:2188	ENSG00000111799	Q99715	Collagen alpha-1(XII) chain	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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: 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)
COL12A1	Antibody/Immunoglobulin	yes		VWF_A, FN3_dom, Collagen

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
calcaneal tendon	1
cartilage tissue	1
tibia	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COL12A1	240	ubiquitous	marker	tibia, calcaneal tendon, cartilage tissue

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COL12A1	2,219

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
COL12A1	Q99715	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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×	0.006	COL12A1
Assembly of collagen fibrils and other multimeric structures	1	200.3×	0.006	COL12A1
Collagen degradation	1	175.7×	0.006	COL12A1
Collagen biosynthesis and modifying enzymes	1	170.4×	0.006	COL12A1

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
endodermal cell differentiation	1	495.6×	0.006	COL12A1
collagen fibril organization	1	224.7×	0.007	COL12A1
cell adhesion	1	37.5×	0.027	COL12A1

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
COL12A1	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	COL12A1
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)
COL12A1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.