LAMA5

Chr 20AR

laminin subunit alpha 5

NCBI Gene: 3911ENSG00000130702UniProt: O15230

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. Plays a role in the regulation of skeletogenesis, through a mechanism that involves integrin-mediated signaling and PTK2B/PYK2 (PubMed:33242826)

Primary Disease Associations & Inheritance

?Bent bone dysplasia syndrome 2MIM #620076
AR
Nephrotic syndrome, type 26MIM #620049
AR
520
ClinVar variants
8
Pathogenic / LP
0.01
pLI score
0
Active trials
Clinical Summary— LAMA5
🧬
Gene-Disease Validity (ClinGen)
LAMA5-related multisystemic syndrome · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.
📋
ClinVar Variants
8 Pathogenic / Likely Pathogenic· 237 VUS of 520 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.31LOEUF
pLI 0.006
Z-score 9.48
OE 0.24 (0.19–0.31)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

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.
-0.27Z-score
OE missense 1.02 (0.98–1.05)
2301 obs / 2264.6 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.0.24 (0.19–0.31)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.02 (0.98–1.05)
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.1.26
0≤1.21.6
LoF obs/exp: 44 / 182.1Missense obs/exp: 2301 / 2264.6Syn Z: -6.45

ClinVar Variant Classifications

520 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2
Likely Pathogenic6
VUS237
Likely Benign259
Benign12
Conflicting4
2
Pathogenic
6
Likely Pathogenic
237
VUS
259
Likely Benign
12
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
0
0
2
Likely Pathogenic
1
3
2
0
6
VUS
5
220
11
1
237
Likely Benign
0
16
94
149
259
Benign
0
3
4
5
12
Conflicting
—4
Total8242111155520

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

View in ClinVar →

Protein Context — Lollipop Plot

LAMA5 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
LAMININ, ALPHA-5; LAMA5
MIM #601033 · *

?Bent bone dysplasia syndrome 2

MIM #620076

Molecular basis of disorder known

Autosomal recessive

Nephrotic syndrome, type 26

MIM #620049

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — LAMA5
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Clinical and Pathologic Features of Congenital Myasthenic Syndromes Caused by 35 Genes-A Comprehensive Review.
Ohno K et al.·Int J Mol Sci
2023Review
Pathogenic LAMA5 Variants and Kidney Disease.
Savige J et al.·Kidney360
2021
A heterozygous LAMA5 variant may contribute to slowly progressive, vinculin-enhanced familial FSGS and pulmonary defects.
Kaimori JY et al.·JCI Insight
2022
A presynaptic congenital myasthenic syndrome attributed to a homozygous sequence variant in LAMA5.
Maselli RA et al.·Ann N Y Acad Sci
2018Review
Genetic variants in the LAMA5 gene in pediatric nephrotic syndrome.
Braun DA et al.·Nephrol Dial Transplant
2019
Association of a common LAMA5 variant with anthropometric and metabolic traits in an Italian cohort of healthy elderly subjects.
De Luca M et al.·Exp Gerontol
2011Cohort
Clear Evidence of LAMA5 Gene Biallelic Truncating Variants Causing Infantile Nephrotic Syndrome.
Taniguchi Y et al.·Kidney360
2021
COL4A5 and LAMA5 variants co-inherited in familial hematuria: digenic inheritance or genetic modifier effect?
Voskarides K et al.·BMC Nephrol
2018Case report
Non-collagen genes role in digenic Alport syndrome.
Daga S et al.·BMC Nephrol
2019
Abnormal Wnt and PI3Kinase signaling in the malformed intestine of lama5 deficient mice.
Ritié L et al.·PLoS One
2012
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Integrated Mendelian randomization analysis reveals causal relationship between LAMA5 and bladder cancer and its metabolic mechanisms.
Wang R et al.·Contemp Oncol (Pozn)
2025🔓 Open AccessFunctional
The role of LAMA5 in breast cancer progression and its potential in immunotherapy.
Zhang X et al.·Discov Oncol
2025🔓 Open Access
Chronic Psychological Stress Induces Cardiomyocyte Hypertrophy Through Corticosterone-Glucocorticoid Receptor-LAMA5 Axis.
Zhang C et al.·Adv Sci (Weinh)
2025🔓 Open Access
MAZ-mediated LAMA5 transcription activation promotes gastric cancer progression through the STAT3 signaling.
Wang Y et al.·Funct Integr Genomics
2025🔓 Open Access
Cancer-Associated Fibroblast Induces Acinar-to-Ductal Cell Transdifferentiation and Pancreatic Cancer Initiation Via LAMA5/ITGA4 Axis.
Parte S et al.·Gastroenterology
2024
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools