LAMB1

laminin subunit beta 1, the group of Laminin subunits

Basic information

Region (hg38): 7:107923799-108003213

Previous symbols: [ "CLM" ]

Links

ENSG00000091136

∙ NCBI:3912 ∙ OMIM:150240 ∙ HGNC:6486 ∙ Uniprot:P07942 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

cobblestone lissencephaly without muscular or ocular involvement (Strong), mode of inheritance: AR
cobblestone lissencephaly without muscular or ocular involvement (Strong), mode of inheritance: AR
cobblestone lissencephaly without muscular or ocular involvement (Moderate), mode of inheritance: AR
cobblestone lissencephaly without muscular or ocular involvement (Strong), mode of inheritance: AR
cobblestone lissencephaly without muscular or ocular involvement (Supportive), mode of inheritance: AR
cobblestone lissencephaly without muscular or ocular involvement (Strong), mode of inheritance: AR
cobblestone lissencephaly without muscular or ocular involvement (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Lissencephaly 5	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic; Ophthalmologic	23472759; 25925986

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LAMB1 gene.

not_provided (732 variants)
Inborn_genetic_diseases (229 variants)
not_specified (73 variants)
LAMB1-related_disorder (59 variants)
Cobblestone_lissencephaly_without_muscular_or_ocular_involvement (49 variants)
Multiple_sclerosis (2 variants)
Intellectual_disability (2 variants)
Autism_spectrum_disorder (1 variants)
Classic_lissencephaly (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LAMB1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000002291.3. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar	161 clinvar	14 clinvar	179
missense	2 clinvar	1 clinvar	475 clinvar	31 clinvar	5 clinvar	514
nonsense	10 clinvar	4 clinvar	2 clinvar			16
start loss						0
frameshift	8 clinvar	6 clinvar	8 clinvar			22
splice donor/acceptor (+/-2bp)	2 clinvar	6 clinvar	3 clinvar			11
Total	22	17	492	192	19

Highest pathogenic variant AF is 0.000119566

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LAMB1	protein_coding	protein_coding	ENST00000222399	33	79457

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.07e-22	1.00	125606	0	142	125748	0.000565

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.544	965	1.01e+3	0.952	0.0000569	11805
Missense in Polyphen		327	394.45	0.82901		4417
Synonymous	0.185	375	380	0.988	0.0000230	3260
Loss of Function	4.64	53	104	0.509	0.00000617	1163

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000880	0.000880
Ashkenazi Jewish	0.000697	0.000695
East Asian	0.000383	0.000381
Finnish	0.000280	0.000277
European (Non-Finnish)	0.000697	0.000695
Middle Eastern	0.000383	0.000381
South Asian	0.000426	0.000425
Other	0.000489	0.000489

dbNSFP

Source: dbNSFP

Function: FUNCTION: 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. Involved in the organization of the laminar architecture of cerebral cortex. It is probably required for the integrity of the basement membrane/glia limitans that serves as an anchor point for the endfeet of radial glial cells and as a physical barrier to migrating neurons. Radial glial cells play a central role in cerebral cortical development, where they act both as the proliferative unit of the cerebral cortex and a scaffold for neurons migrating toward the pial surface. {ECO:0000269|PubMed:23472759}.;
Disease: DISEASE: Lissencephaly 5 (LIS5) [MIM:615191]: An autosomal recessive brain malformation characterized by cobblestone changes in the cortex, more severe in the posterior region, and subcortical band heterotopia. Affected individuals have hydrocephalus, seizures, and severely delayed psychomotor development. {ECO:0000269|PubMed:23472759}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);ECM-receptor interaction - Homo sapiens (human);Focal adhesion - Homo sapiens (human);Small cell lung cancer - Homo sapiens (human);Amoebiasis - Homo sapiens (human);Toxoplasmosis - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Alpha 6 Beta 4 signaling pathway;Human Complement System;Focal Adhesion;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;Inflammatory Response Pathway;Developmental Biology;Signal Transduction;prion pathway;Post-translational protein phosphorylation;Alpha6Beta4Integrin;Laminin interactions;Post-translational protein modification;Metabolism of proteins;Extracellular matrix organization;Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs);Beta3 integrin cell surface interactions;agrin in postsynaptic differentiation;Degradation of the extracellular matrix;a6b1 and a6b4 Integrin signaling;L1CAM interactions;Non-integrin membrane-ECM interactions;Axon guidance;ECM proteoglycans;MET activates PTK2 signaling;MET promotes cell motility;Signaling by MET;Signaling by Receptor Tyrosine Kinases;Beta1 integrin cell surface interactions;Alpha6 beta4 integrin-ligand interactions (Consensus)

Recessive Scores

pRec: 0.501

Intolerance Scores

loftool: 0.631
rvis_EVS: -0.99
rvis_percentile_EVS: 8.55

Haploinsufficiency Scores

pHI: 0.839
hipred: Y
hipred_score: 0.589
ghis: 0.582

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.915

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Lamb1
Phenotype: muscle phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan);

Zebrafish Information Network

Gene name: lamb1a
Affected structure: fast muscle myoblast
Phenotype tag: abnormal
Phenotype quality: decreased length

Gene ontology

Biological process: cell adhesion;neuronal-glial interaction involved in cerebral cortex radial glia guided migration;extracellular matrix organization;positive regulation of cell migration;neuron projection development;substrate adhesion-dependent cell spreading;endodermal cell differentiation;odontogenesis;post-translational protein modification;cellular protein metabolic process;positive regulation of epithelial cell proliferation
Cellular component: extracellular region;basement membrane;laminin-1 complex;laminin-2 complex;extracellular space;endoplasmic reticulum lumen;laminin-8 complex;laminin-10 complex;perinuclear region of cytoplasm;collagen-containing extracellular matrix;extracellular exosome
Molecular function: structural molecule activity;extracellular matrix structural constituent;protein binding