LAMB1

Chr 7ARAD

laminin subunit beta 1

Also known as: CLM, LIS5, LKBMH, LUCAO

The LAMB1 protein is the beta-1 chain of laminin-1, a major basement membrane glycoprotein that mediates cell adhesion, migration, and signaling in the extracellular matrix. Mutations cause leukoencephalopathy with variable cortical brain malformations and/or hydrocephalus as well as adult-onset leukoencephalopathy without lacunae, inherited in both autosomal recessive and autosomal dominant patterns. The pathogenic mechanism involves gain-of-function effects that disrupt normal basement membrane structure and function.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismAR/ADLOEUF 0.642 OMIM phenotypes
Clinical SummaryLAMB1
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Gene-Disease Validity (ClinGen)
cobblestone lissencephaly without muscular or ocular involvement · ARModerate

Moderate evidence — consider for supplementary testing

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📖
GeneReview available — LAMB1
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
0.64LOEUF
pLI 0.000
Z-score 4.64
OE 0.51 (0.410.64)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.54Z-score
OE missense 0.95 (0.901.00)
965 obs / 1013.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.51 (0.410.64)
00.351.4
Missense OE0.95 (0.901.00)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 53 / 104.1Missense obs/exp: 965 / 1013.7Syn Z: 0.19
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongLAMB1-related cobblestone brain malformation without muscular or ocular abnormalitiesLOFAR

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

DN
0.6938th %ile
GOF
0.77top 25%
LOF
0.2190th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

LAMB1 · 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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