LAMA2-related muscular dystrophy

Summary

LAMA2-related muscular dystrophy (MONDO:0100228) is a disease caused by LAMA2 (GenCC Strong), with 1 cohort gene and 1 clinical trial.

At a glance

• Causal gene: LAMA2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 4,275
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	LAMA2-related muscular dystrophy
Mondo ID	MONDO:0100228
UMLS	C5679788
MedGen	1826054
GARD	0026089
Is cancer (heuristic)	no

Also known as: LAMA2-related muscular dystrophy

Data availability: 4,275 ClinVar variants · 1 GenCC gene-disease record.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › musculoskeletal system disorder › muscle tissue disorder › skeletal muscle disorder › myopathy › muscular dystrophy › LAMA2-related muscular dystrophy

Related subtypes (10): muscular dystrophy, Barnes type, muscular dystrophy, cardiac type, muscular dystrophy, Hemizygous lethal type, muscular dystrophy, Mabry type, muscular dystrophy, progressive Pectorodorsal, progressive muscular dystrophy, distal myopathy, congenital muscular dystrophy, Fukuda-Miyanomae-Nakata syndrome, DMD-related muscular dystrophy

Subtypes (2): congenital merosin-deficient muscular dystrophy 1A, muscular dystrophy, limb-girdle, autosomal recessive 23

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:

415 likely benign, 88 uncertain significance, 40 pathogenic, 20 conflicting classifications of pathogenicity, 10 pathogenic/likely pathogenic, 10 likely pathogenic, 10 benign, 7 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1017561	NM_000426.4(LAMA2):c.4860G>A (p.Lys1620=)	LAMA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1028256	NM_000426.4(LAMA2):c.7898+1G>A	LAMA2	Pathogenic	criteria provided, multiple submitters, no conflicts
1066222	NM_000426.4(LAMA2):c.3037+1G>T	LAMA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1066310	NM_000426.4(LAMA2):c.4860+2T>C	LAMA2	Pathogenic	criteria provided, single submitter
1068853	NM_000426.4(LAMA2):c.5795_5804del (p.Lys1932fs)	LAMA2	Pathogenic	criteria provided, single submitter
1069078	NM_000426.4(LAMA2):c.4368T>A (p.Tyr1456Ter)	LAMA2	Pathogenic	criteria provided, single submitter
1069086	NM_000426.4(LAMA2):c.7393_7394del (p.Ala2464_Asp2465insTer)	LAMA2	Pathogenic	criteria provided, single submitter
1069113	NM_000426.4(LAMA2):c.8541del (p.Trp2847fs)	LAMA2	Pathogenic	criteria provided, single submitter
1069271	NM_000426.4(LAMA2):c.2500G>T (p.Gly834Ter)	LAMA2	Pathogenic	criteria provided, single submitter
1069368	NM_000426.4(LAMA2):c.4523G>C (p.Arg1508Thr)	LAMA2	Pathogenic	criteria provided, single submitter
1069372	NM_000426.4(LAMA2):c.9191dup (p.Phe3065fs)	LAMA2	Pathogenic	criteria provided, single submitter
1069413	NM_000426.4(LAMA2):c.2520dup (p.Gly841fs)	LAMA2	Pathogenic	criteria provided, single submitter
1069560	NC_000006.11:g.(?129837325)(129837502_?)del	LAMA2	Pathogenic	criteria provided, single submitter
1069561	NC_000006.11:g.(?129486711)(129486830_?)del	LAMA2	Pathogenic	criteria provided, single submitter
1069803	NM_000426.4(LAMA2):c.910-1G>A	LAMA2	Pathogenic	criteria provided, single submitter
1070507	NM_000426.4(LAMA2):c.6993-2A>G	LAMA2	Pathogenic	criteria provided, single submitter
1070781	NM_000426.4(LAMA2):c.8748del (p.Glu2917fs)	LAMA2	Pathogenic	criteria provided, multiple submitters, no conflicts
1071850	NM_000426.4(LAMA2):c.1824T>G (p.Tyr608Ter)	LAMA2	Pathogenic	criteria provided, single submitter
1072322	NM_000426.4(LAMA2):c.2042T>A (p.Leu681Ter)	LAMA2	Pathogenic	criteria provided, single submitter
1072450	NM_000426.4(LAMA2):c.6573del (p.Phe2191fs)	LAMA2	Pathogenic	criteria provided, single submitter
1072865	NM_000426.4(LAMA2):c.5602G>T (p.Glu1868Ter)	LAMA2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1073098	NM_000426.4(LAMA2):c.3700_3701insTTTTTTTTTTTTTTTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCGCCCAGGTCGGACTGCGGACTGCAGTGGCGCAATCTCGGCTCACTGCAAGCTCCGCTTCCCGGGTTCACGCCATTCTCCTGCCTCAGCCTCCCGAGTAGCTGGGACTACAGGCGCCCGCCACCGCGCCCGGCTAATTTTTTGTATTTTTAGTAGAGACGGGGTTTCACCTTGTTAGCCAGGATGGTCTCGATCTCCTGACCTCATGATCCACCGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCGCGCCCGGCCGGAACCTTTT (p.Tyr1234delinsPhePhePhePhePhePhePhePheTer)	LAMA2	Pathogenic	criteria provided, single submitter
1073388	NM_000426.4(LAMA2):c.3300C>A (p.Tyr1100Ter)	LAMA2	Pathogenic	criteria provided, single submitter
1073988	NM_000426.4(LAMA2):c.3332del (p.Pro1111fs)	LAMA2	Pathogenic	criteria provided, single submitter
1074303	NM_000426.4(LAMA2):c.652_653del (p.Leu218fs)	LAMA2	Pathogenic	criteria provided, single submitter
1074594	NM_000426.4(LAMA2):c.3700_3701insTTTTTTTTTTNNNNNNNNNNAGGATGGTCTCGATCTCCTGACCTCATGATCCACCCGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCGCGCCCGGCCGGAACCTTTTT (p.Tyr1234delinsPhePhePheXaaXaaXaaXaaArgMetValSerIleSerTer)	LAMA2	Pathogenic	criteria provided, single submitter
1074786	NM_000426.4(LAMA2):c.6964del (p.Glu2322fs)	LAMA2	Pathogenic	criteria provided, single submitter
1074894	NM_000426.4(LAMA2):c.3874del (p.Ala1292fs)	LAMA2	Pathogenic	criteria provided, single submitter
1075019	NM_000426.4(LAMA2):c.7814del (p.Thr2605fs)	LAMA2	Pathogenic	criteria provided, single submitter
1075439	NM_000426.4(LAMA2):c.4814_4830del (p.Pro1605fs)	LAMA2	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · Orphanet: 2 · 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
LAMA2	Definitive	Autosomal recessive	congenital merosin-deficient muscular dystrophy 1A	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LAMA2	Orphanet:258	Laminin subunit alpha 2-related congenital muscular dystrophy
LAMA2	Orphanet:565837	Laminin subunit alpha 2-related limb-girdle muscular dystrophy R23

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
LAMA2	HGNC:6482	ENSG00000196569	P24043	Laminin subunit alpha-2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LAMA2	Laminin subunit alpha-2	Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · 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	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
LAMA2	Other/Unknown	no		Laminin_IV, EGF, Laminin_G

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
mucosa of stomach	1
right ovary	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LAMA2	272	ubiquitous	marker	mucosa of stomach, calcaneal tendon, right ovary

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LAMA2	2,688

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
LAMA2	P24043	2

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 15. 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
MET promotes cell motility	1	601.0×	0.007	LAMA2
Attachment of bacteria to epithelial cells	1	496.5×	0.007	LAMA2
Laminin interactions	1	380.7×	0.007	LAMA2
MET activates PTK2 signaling	1	380.7×	0.007	LAMA2
EGR2 and SOX10-mediated initiation of Schwann cell myelination	1	368.4×	0.007	LAMA2
Signaling by MET	1	317.2×	0.007	LAMA2
Formation of the dystrophin-glycoprotein complex (DGC)	1	308.6×	0.007	LAMA2
Developmental Lineage of Pancreatic Ductal Cells	1	228.4×	0.008	LAMA2
Non-integrin membrane-ECM interactions	1	154.3×	0.010	LAMA2
ECM proteoglycans	1	150.3×	0.010	LAMA2
Extracellular matrix organization	1	63.1×	0.022	LAMA2
Signaling by Receptor Tyrosine Kinases	1	51.7×	0.024	LAMA2
Nervous system development	1	42.9×	0.027	LAMA2
Developmental Biology	1	14.5×	0.074	LAMA2
Signal Transduction	1	10.2×	0.098	LAMA2

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
positive regulation of synaptic transmission, cholinergic	1	3370.4×	0.002	LAMA2
regulation of basement membrane organization	1	2808.7×	0.002	LAMA2
Schwann cell differentiation	1	2407.4×	0.002	LAMA2
positive regulation of integrin-mediated signaling pathway	1	1296.3×	0.002	LAMA2
positive regulation of muscle cell differentiation	1	1123.5×	0.002	LAMA2
maintenance of blood-brain barrier	1	481.5×	0.004	LAMA2
regulation of embryonic development	1	330.4×	0.005	LAMA2
positive regulation of cell adhesion	1	271.8×	0.006	LAMA2
muscle organ development	1	166.8×	0.008	LAMA2
regulation of cell migration	1	157.5×	0.008	LAMA2
axon guidance	1	90.6×	0.012	LAMA2
cell adhesion	1	37.5×	0.027	LAMA2

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
LAMA2	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	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	LAMA2

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)
LAMA2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06132750	Not specified	RECRUITING	A 5-year Natural History Study in LAMA2-related Muscular Dystrophy and SELENON-related Myopathy.