LAMC3

Chr 9AR

laminin subunit gamma 3

NCBI Gene: 10319ENSG00000050555UniProt: Q9Y6N6

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

Cortical malformations, occipitalMIM #614115
AR
691
ClinVar variants
58
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— LAMC3
🧬
Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder · ADDisputed

Disputed — evidence questions this relationship

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
58 Pathogenic / Likely Pathogenic· 342 VUS of 691 total submissions

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.
0.84LOEUF
pLI 0.000
Z-score 2.67
OE 0.66 (0.52–0.84)
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.
-0.43Z-score
OE missense 1.04 (0.98–1.10)
965 obs / 928.1 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.0.66 (0.52–0.84)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.04 (0.98–1.10)
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.1.01
0≤1.21.6
LoF obs/exp: 48 / 72.6Missense obs/exp: 965 / 928.1Syn Z: -0.13

ClinVar Variant Classifications

691 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic40
Likely Pathogenic18
VUS342
Likely Benign282
Benign1
Conflicting8
40
Pathogenic
18
Likely Pathogenic
342
VUS
282
Likely Benign
1
Benign
8
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
17
0
23
0
40
Likely Pathogenic
15
0
3
0
18
VUS
3
310
25
4
342
Likely Benign
0
2
104
176
282
Benign
0
0
1
0
1
Conflicting
—8
Total35312156180691

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

View in ClinVar →

Protein Context — Lollipop Plot

LAMC3 · protein map & ClinVar variants

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

Gene2Phenotype Curations

LAMC3-related occipital cortical malformations

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, GAMMA-3; LAMC3
MIM #604349 · *

Cortical malformations, occipital

MIM #614115

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.
O'Roak BJ et al.·Nature
2012
Novel LAMC3 pathogenic variant enriched in Finnish population causes malformations of cortical development and severe epilepsy.
Saarela A et al.·Epileptic Disord
2024Case report
LAMC3 interference reduces drug resistance of carboplatin-resistant ovarian cancer cells.
Liu X et al.·Sci Rep
2025
A novel splice variant expands the LAMC3-associated cortical phenotype to frontal only polymicrogyria and adult-onset epilepsy.
Kasper BS et al.·Am J Med Genet A
2020Case report
A novel mutation in LAMC3 associated with generalized polymicrogyria of the cortex and epilepsy.
Zambonin JL et al.·Neurogenetics
2018Case report
[Relationships between decreased LAMC3 and poor prognosis in ovarian cancer].
Lei SM et al.·Zhonghua Fu Chan Ke Za Zhi
2021
Compound heterozygous variants in LAMC3 in association with posterior periventricular nodular heterotopia.
De Angelis C et al.·BMC Med Genomics
2021Case report
Strategies for identifying NUP98 rearrangements in adult myeloid neoplasms.
Yuen LD et al.·Haematologica
2026
Structural analysis and mutation detection strategy for the human LAMC3 gene.
Cserhalmi-Friedman PB et al.·Biochem Biophys Res Commun
2001
Nutritional ketosis modulates the methylation of cancer-related genes in patients with obesity and in breast cancer cells.
Lorenzo PM et al.·J Physiol Biochem
2025Cohort
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

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools