LAMB1

Chr 7ARAD

laminin subunit beta 1

Also known as: CLM, LIS5, LKBMH, LUCAO

Laminins, a family of extracellular matrix glycoproteins, are the major noncollagenous constituent of basement membranes. They have been implicated in a wide variety of biological processes including cell adhesion, differentiation, migration, signaling, neurite outgrowth and metastasis. Laminins are composed of 3 non identical chains: laminin alpha, beta and gamma (formerly A, B1, and B2, respectively) and they form a cruciform structure consisting of 3 short arms, each formed by a different chain, and a long arm composed of all 3 chains. Each laminin chain is a multidomain protein encoded by a distinct gene. Several isoforms of each chain have been described. Different alpha, beta and gamma chain isomers combine to give rise to different heterotrimeric laminin isoforms which are designated by Arabic numerals in the order of their discovery, i.e. alpha1beta1gamma1 heterotrimer is laminin 1. The biological functions of the different chains and trimer molecules are largely unknown, but some of the chains have been shown to differ with respect to their tissue distribution, presumably reflecting diverse functions in vivo. This gene encodes the beta chain isoform laminin, beta 1. The beta 1 chain has 7 structurally distinct domains which it shares with other beta chain isomers. The C-terminal helical region containing domains I and II are separated by domain alpha, domains III and V contain several EGF-like repeats, and domains IV and VI have a globular conformation. Laminin, beta 1 is expressed in most tissues that produce basement membranes, and is one of the 3 chains constituting laminin 1, the first laminin isolated from Engelbreth-Holm-Swarm (EHS) tumor. A sequence in the beta 1 chain that is involved in cell attachment, chemotaxis, and binding to the laminin receptor was identified and shown to have the capacity to inhibit metastasis. [provided by RefSeq, Aug 2011]

GeneReviewsOMIMResearchGenerating clinical summary…
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.
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ClinVar Variants
51 unique Pathogenic / Likely Pathogenic· 577 VUS of 1148 total submissions
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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 OE?0.51 (0.410.64)
00.351.4
Missense OE?0.95 (0.901.00)
00.61.4
Synonymous OE?0.99
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

This gene — mechanism propensity

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

1148 submitted variants in ClinVar

Classification Summary

Pathogenic34
Likely Pathogenic17
VUS577
Likely Benign349
Benign117
Conflicting24
34
Pathogenic
17
Likely Pathogenic
577
VUS
349
Likely Benign
117
Benign
24
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
25
1
8
0
34
Likely Pathogenic
16
1
0
0
17
VUS
11
537
25
4
577
Likely Benign
0
13
162
174
349
Benign
0
8
90
19
117
Conflicting
24
Total525602851971,118

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

View in ClinVar →

22 pathogenic / likely-pathogenic (of 26) ClinVar copy-number / structural variants overlap LAMB1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

LAMB1 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →