LAMC3

Chr 9AR

laminin subunit gamma 3

Also known as: OCCM

Encodes the gamma-3 chain of laminin, an extracellular matrix glycoprotein that mediates cell attachment, migration and organization during embryonic development, particularly at basement membranes of the dermal-epidermal junction and ciliated epithelial surfaces. Mutations cause cortical malformations affecting the occipital region through autosomal recessive inheritance. This gene shows tolerance to loss-of-function variants in the population, which may contribute to the recessive inheritance pattern observed clinically.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 0.841 OMIM phenotype
Clinical SummaryLAMC3
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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.
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ClinVar Variants
20 unique Pathogenic / Likely Pathogenic· 80 VUS of 200 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.84LOEUF
pLI 0.000
Z-score 2.67
OE 0.66 (0.520.84)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.43Z-score
OE missense 1.04 (0.981.10)
965 obs / 928.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.66 (0.520.84)
00.351.4
Missense OE1.04 (0.981.10)
00.61.4
Synonymous OE1.01
01.21.6
LoF obs/exp: 48 / 72.6Missense obs/exp: 965 / 928.1Syn Z: -0.13
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveLAMC3-related occipital cortical malformationsLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6937th %ile
GOF
0.78top 25%
LOF
0.2289th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

200 submitted variants in ClinVar

Classification Summary

Pathogenic14
Likely Pathogenic6
VUS80
Likely Benign100
14
Pathogenic
6
Likely Pathogenic
80
VUS
100
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
9
0
5
0
14
Likely Pathogenic
6
0
0
0
6
VUS
0
73
5
2
80
Likely Benign
0
1
41
58
100
Benign
0
0
0
0
0
Total15745160200

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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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