LAMA2

Chr 6AR

laminin subunit alpha 2

NCBI Gene: 3908ENSG00000196569UniProt: P24043

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

Primary Disease Associations & Inheritance

Muscular dystrophy, congenital, merosin deficient or partially deficientMIM #607855
AR
Muscular dystrophy, limb-girdle, autosomal recessive 23MIM #618138
AR
UniProtMerosin-deficient congenital muscular dystrophy 1A
5565
ClinVar variants
85
Pathogenic / LP
0.00
pLI score
4
Active trials
Clinical Summary— LAMA2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
85 Pathogenic / Likely Pathogenic· 240 VUS of 5565 total submissions
💊
Clinical Trials
4 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.73LOEUF
pLI 0.000
Z-score 4.50
OE 0.62 (0.53–0.73)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.03Z-score
OE missense 1.00 (0.96–1.04)
1698 obs / 1694.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.62 (0.53–0.73)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.00 (0.96–1.04)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.07
0≤1.21.6
LoF obs/exp: 102 / 164.3Missense obs/exp: 1698 / 1694.5Syn Z: -1.44

ClinVar Variant Classifications

5565 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic53
Likely Pathogenic32
VUS240
Likely Benign136
Benign5
Conflicting3
53
Pathogenic
32
Likely Pathogenic
240
VUS
136
Likely Benign
5
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
24
0
29
0
53
Likely Pathogenic
20
2
10
0
32
VUS
3
215
18
4
240
Likely Benign
0
6
71
59
136
Benign
0
1
3
1
5
Conflicting
—3
Total4722413164469

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

LAMA2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

LAMA2-related congenital muscular dystrophy

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
LAMININ, ALPHA-2; LAMA2
MIM #156225 · *

Muscular dystrophy, congenital, merosin deficient or partially deficient

MIM #607855

Molecular basis of disorder known

Autosomal recessive

Muscular dystrophy, limb-girdle, autosomal recessive 23

MIM #618138

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Congenital muscular dystrophies in the UK population: Clinical and molecular spectrum of a large cohort diagnosed over a 12-year period.
Sframeli M et al.·Neuromuscul Disord
2017Cohort
Serine biosynthesis as a novel therapeutic target for dilated cardiomyopathy.
Perea-Gil I et al.·Eur Heart J
2022
LAMA2 gene mutation update: Toward a more comprehensive picture of the laminin-α2 variome and its related phenotypes.
Oliveira J et al.·Hum Mutat
2018Review
Cohort Expansion and Genotype-Phenotype Analysis of RAB11A-Associated Neurodevelopmental Disorder.
Borroto MC et al.·Pediatr Neurol
2024Cohort
Epilepsy in LAMA2-related muscular dystrophy: A systematic review of the literature.
Salvati A et al.·Seizure
2021Review
Hypoglycemia in Patients With LAMA2-CMD.
Camelo CG et al.·Pediatr Neurol
2023Cohort
Extracellular matrix-driven congenital muscular dystrophies.
Mohassel P et al.·Matrix Biol
2018Review
Noncoding variants are a rare cause of recessive developmental disorders in trans with coding variants.
Lord J et al.·Genet Med
2024
A novel mouse model for LAMA2-related muscular dystrophy with analysis of molecular pathogenesis and clinical phenotype.
Tan D et al.·Elife
2025Functional
Congenital muscular dystrophies: What is new?
Zambon AA et al.·Neuromuscul Disord
2021Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Bacteria in Breast Milk

Metagenomic Analysis of Bacterial Microbiota in Breast Milk

RECRUITING
NCT06037421Centre Hospitalier Sud FrancilienStarted 2025-09-08
Human breast milk samplingSaddle samplingSkin sampling
Muscular Dystrophy

Clinical Trial Readiness for the Dystroglycanopathies

RECRUITING
NCT00313677Katherine MathewsStarted 2006-04
LAMA2-related Muscular DystrophySELENON-related Myopathy

A 5-year Natural History Study in LAMA2-related Muscular Dystrophy and SELENON-related Myopathy.

RECRUITING
NCT06132750Radboud University Medical CenterStarted 2023-10-06
No intervention
LaminopathiesEmery Dreifuss Muscular Dystrophy 2LMNA-Related Congenital Muscular Dystrophy

Modifying Factors in Striated Muscle Laminopathies

RECRUITING
NCT05394506Phase NAInstitut National de la Santé Et de la Recherche Médicale, FranceStarted 2022-09-08
Skin BiopsyMuscle biopsy

External Resources

Links to major genomics databases and tools