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 (12 variants)
• Cobblestone lissencephaly without muscular or ocular involvement (3 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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	144	17	163
missense			341	12	10	363
nonsense	7	2	1			10
start loss						0
frameshift	6	6	5			17
inframe indel			5			5
splice donor/acceptor (+/-2bp)	1	3	2			6
splice region			8	29	4	41
non coding			4	116	86	206
Total	14	11	360	272	113

Highest pathogenic variant AF is 0.00000657

Variants in LAMB1

This is a list of pathogenic ClinVar variants found in the LAMB1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
7-107923866-T-C			Likely benign (Jun 26, 2018)
7-107923921-T-G			Benign (Jun 19, 2018)
7-107923964-C-T			Uncertain significance (Aug 03, 2022)
7-107923965-T-C		Cobblestone lissencephaly without muscular or ocular involvement	Uncertain significance (Dec 01, 2022)
7-107923971-C-T			Uncertain significance (Jul 22, 2023)
7-107923976-A-G			Uncertain significance (Jul 31, 2023)
7-107923987-T-A		not specified	Likely benign (May 24, 2017)
7-107923996-T-A			Likely benign (Apr 09, 2023)
7-107923998-G-A			Likely benign (May 24, 2022)
7-107924003-G-A			Uncertain significance (Jan 18, 2024)
7-107924007-G-A		Inborn genetic diseases	Uncertain significance (Jul 14, 2023)
7-107924030-A-C			Uncertain significance (Nov 01, 2022)
7-107924035-T-A		Inborn genetic diseases	Uncertain significance (Oct 05, 2023)
7-107924040-C-A			Uncertain significance (Aug 09, 2021)
7-107924040-C-T			Uncertain significance (Mar 01, 2017)
7-107924044-A-G		not specified	Likely benign (Sep 19, 2016)
7-107924055-A-ATCTT			Uncertain significance (Jul 28, 2023)
7-107924062-A-G		LAMB1-related disorder	Likely benign (Apr 29, 2022)
7-107924065-G-A		not specified	Benign (Dec 30, 2023)
7-107924066-TC-T			Uncertain significance (Dec 30, 2023)
7-107924085-A-T			Uncertain significance (Mar 22, 2022)
7-107924091-TGG-T		not specified	Benign (Jan 19, 2024)
7-107924093-GGGAGAT-G			Likely benign (Nov 24, 2023)
7-107924094-G-A		Maple syrup urine disease • Pyruvate dehydrogenase complex deficiency • Leigh syndrome • not specified • Cobblestone lissencephaly without muscular or ocular involvement	Benign (Feb 01, 2024)
7-107924095-G-T			Conflicting classifications of pathogenicity (Nov 17, 2023)

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