LAMA3

Chr 18AR

laminin subunit alpha 3

Also known as: BM600, E170, JEB2A, JEB2B, JEB2C, LAMNA, LOCS

The LAMA3 protein is a laminin alpha subunit that forms part of heterotrimeric laminin complexes essential for basement membrane formation and function, mediating cell attachment, migration, and tissue organization during development. Mutations cause autosomal recessive junctional epidermolysis bullosa with a spectrum of severity from intermediate (type 2A) to severe (type 2B) forms, as well as laryngoonychocutaneous syndrome (type 2C) which involves skin, laryngeal, and nail abnormalities. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.69), and these conditions typically present in the neonatal period with skin fragility and blistering.

Summary from RefSeq, OMIM, UniProt
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Primary Disease Associations & Inheritance

Epidermolysis bullosa, junctional 2A, intermediateMIM #619783
AR
Epidermolysis bullosa, junctional 2B, severeMIM #619784
AR
Epidermolysis bullosa, junctional 2C, laryngoonychocutaneousMIM #245660
AR
1
Active trials
30
Pubs (1 yr)
35
P/LP submissions
3%
P/LP missense
0.69
LOEUF
LOF
Mechanism· G2P
Clinical SummaryLAMA3
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
34 unique Pathogenic / Likely Pathogenic· 257 VUS of 400 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
📖
GeneReview available — LAMA3
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.69LOEUF
pLI 0.000
Z-score 5.05
OE 0.59 (0.500.69)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.49Z-score
OE missense 0.97 (0.931.01)
1752 obs / 1810.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.59 (0.500.69)
00.351.4
Missense OE0.97 (0.931.01)
00.61.4
Synonymous OE0.98
01.21.6
LoF obs/exp: 102 / 173.9Missense obs/exp: 1752 / 1810.3Syn Z: 0.37
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveLAMA3-related laryngoonychocutaneous syndromeLOFAR

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

DN
0.7229th %ile
GOF
0.6150th %ile
LOF
0.2483th %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

400 submitted variants in ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic28
VUS257
Likely Benign65
Benign1
6
Pathogenic
28
Likely Pathogenic
257
VUS
65
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
5
0
6
Likely Pathogenic
22
1
4
1
28
VUS
0
249
8
0
257
Likely Benign
0
12
32
21
65
Benign
0
0
1
0
1
Total232625022357

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

View in ClinVar →

Protein Context — Lollipop Plot

LAMA3 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗