LAMB3

laminin subunit beta 3, the group of Laminin subunits|MicroRNA protein coding host genes

Basic information

Region (hg38): 1:209614870-209652425

Previous symbols: [ "LAMNB1" ]

Links

ENSG00000196878 ∙ NCBI:3914 ∙ OMIM:150310 ∙ HGNC:6490 ∙ Uniprot:Q13751 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• junctional epidermolysis bullosa (Definitive), mode of inheritance: AR
• junctional epidermolysis bullosa Herlitz type (Strong), mode of inheritance: AR
• junctional epidermolysis bullosa, non-Herlitz type (Strong), mode of inheritance: AR
• junctional epidermolysis bullosa, non-Herlitz type (Definitive), mode of inheritance: AR
• junctional epidermolysis bullosa Herlitz type (Definitive), mode of inheritance: AR
• amelogenesis imperfecta type 1A (Moderate), mode of inheritance: AD
• junctional epidermolysis bullosa, non-Herlitz type (Strong), mode of inheritance: AR
• generalized junctional epidermolysis bullosa non-Herlitz type (Supportive), mode of inheritance: AR
• junctional epidermolysis bullosa Herlitz type (Supportive), mode of inheritance: AR
• amelogenesis imperfecta type 1 (Supportive), mode of inheritance: AD
• junctional epidermolysis bullosa Herlitz type (Definitive), mode of inheritance: AR
• amelogenesis imperfecta type 1A (Strong), mode of inheritance: AD
• junctional epidermolysis bullosa Herlitz type (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Epidermolysis bullosa, junctional 1B, severe	AR	Dermatologic	Epidermolysis bullosa, junctional 1B, severe involves a severe and sometimes fatal blistering skin disease, and treatment with autologous transgenic keratinocyte cultures has been described as beneficial	Dental; Dermatologic	7706760; 7774918; 9205497; 9242513; 11023379; 15538630; 16473856; 17476356; 20301304; 19369679; 20301304; 21801158; 23632796; 23958762; 29144448

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LAMB3 gene.

• not provided (112 variants)
• Junctional epidermolysis bullosa gravis of Herlitz (16 variants)
• Junctional epidermolysis bullosa (12 variants)
• Junctional epidermolysis bullosa, non-Herlitz type (10 variants)
• Junctional epidermolysis bullosa gravis of Herlitz;Junctional epidermolysis bullosa, non-Herlitz type;Amelogenesis imperfecta type 1A (4 variants)
• LAMB3-related disorder (4 variants)
• Amelogenesis imperfecta type 1A;Junctional epidermolysis bullosa gravis of Herlitz;Junctional epidermolysis bullosa, non-Herlitz type (3 variants)
• Junctional epidermolysis bullosa gravis of Herlitz;Junctional epidermolysis bullosa, non-Herlitz type (2 variants)
• Junctional epidermolysis bullosa, non-Herlitz type;Junctional epidermolysis bullosa gravis of Herlitz (1 variants)
• Abnormality of the skin (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LAMB3 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	447	13	462
missense	1	4	177	18	13	213
nonsense	52	41				93
start loss		1				1
frameshift	54	51				105
inframe indel			7			7
splice donor/acceptor (+/-2bp)	11	45	2			58
splice region		1	8	66	1	76
non coding	2		11	177	50	240
Total	120	142	199	642	76

Highest pathogenic variant AF is 0.000467

Variants in LAMB3

This is a list of pathogenic ClinVar variants found in the LAMB3 region.

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

Position	Type	Phenotype	Significance	ClinVar
1-209614879-G-A		Junctional epidermolysis bullosa	Uncertain significance (Jan 13, 2018)
1-209614992-C-T		Junctional epidermolysis bullosa	Uncertain significance (Jan 12, 2018)
1-209614996-G-A		Junctional epidermolysis bullosa	Uncertain significance (Jan 12, 2018)
1-209615009-C-T		Junctional epidermolysis bullosa	Likely benign (Jan 12, 2018)
1-209615047-C-T		Junctional epidermolysis bullosa	Uncertain significance (Jan 13, 2018)
1-209615134-A-G		Junctional epidermolysis bullosa	Likely benign (Jan 13, 2018)
1-209615139-C-T		Junctional epidermolysis bullosa	Uncertain significance (Jan 12, 2018)
1-209615147-G-A		Junctional epidermolysis bullosa	Uncertain significance (Apr 27, 2017)
1-209615169-G-A		Junctional epidermolysis bullosa • Amelogenesis imperfecta type 1A • Junctional epidermolysis bullosa, non-Herlitz type • Junctional epidermolysis bullosa gravis of Herlitz	Benign (Jan 08, 2024)
1-209615201-C-T		Junctional epidermolysis bullosa	Likely benign (Jan 13, 2018)
1-209615252-C-T		not specified	Uncertain significance (Jul 17, 2020)
1-209615271-TCA-T		Junctional epidermolysis bullosa gravis of Herlitz	Likely pathogenic (Jan 11, 2016)
1-209615283-G-A			Likely benign (Jun 23, 2023)
1-209615289-G-A			Likely benign (Jan 15, 2024)
1-209615297-C-T		Inborn genetic diseases	Uncertain significance (Aug 13, 2021)
1-209615298-G-A			Likely benign (Jun 04, 2023)
1-209615299-C-T		Inborn genetic diseases	Uncertain significance (Nov 19, 2022)
1-209615300-G-A		Amelogenesis imperfecta type 1A	Uncertain significance (Mar 01, 2023)
1-209615307-G-A			Likely benign (Dec 25, 2023)
1-209615311-T-C		Junctional epidermolysis bullosa	Conflicting classifications of pathogenicity (Jan 30, 2024)
1-209615314-TCACGGATCTGCTC-T		Amelogenesis imperfecta	Pathogenic (-)
1-209615333-G-T		Inborn genetic diseases	Uncertain significance (Feb 23, 2023)
1-209615334-C-T			Likely benign (Jun 15, 2023)
1-209615336-TCTCCAGTC-T		Amelogenesis imperfecta type 1A	Likely pathogenic (Jun 20, 2022)
1-209615337-C-T			Likely benign (Feb 04, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LAMB3	protein_coding	protein_coding	ENST00000391911	22	37597

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.31e-15	1.00	125441	0	307	125748	0.00122

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.525	747	708	1.06	0.0000485	7596
Missense in Polyphen		197	203.93	0.96603		2214
Synonymous	-0.952	297	277	1.07	0.0000180	2356
Loss of Function	3.24	34	61.4	0.554	0.00000345	655

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00182	0.00182
Ashkenazi Jewish	0.000401	0.000397
East Asian	0.000490	0.000489
Finnish	0.000463	0.000462
European (Non-Finnish)	0.00192	0.00192
Middle Eastern	0.000490	0.000489
South Asian	0.000832	0.000817
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.
• Disease: DISEASE: Epidermolysis bullosa, junctional, Herlitz type (H-JEB) [MIM:226700]: An infantile and lethal form of junctional epidermolysis bullosa, a group of blistering skin diseases characterized by tissue separation which occurs within the dermo- epidermal basement In the Herlitz type, death occurs usually within the first six months of life. Occasionally, children survive to teens. It is marked by bullous lesions at birth and extensive denudation of skin and mucous membranes that may be hemorrhagic. {ECO:0000269|PubMed:7550237}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Generalized atrophic benign epidermolysis bullosa (GABEB) [MIM:226650]: A non-lethal, adult form of junctional epidermolysis bullosa characterized by life-long blistering of the skin, associated with hair and tooth abnormalities. {ECO:0000269|PubMed:17476356, ECO:0000269|PubMed:9767254}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Amelogenesis imperfecta 1A (AI1A) [MIM:104530]: A form of amelogenesis imperfecta, a disorder characterized by defective enamel formation. The enamel may be hypoplastic, hypomineralized or both, and affected teeth may be discoloured, sensitive or prone to disintegration. {ECO:0000269|PubMed:23632796, ECO:0000269|PubMed:23958762}. 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;Focal Adhesion;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;Assembly of collagen fibrils and other multimeric structures;Signal Transduction;prion pathway;Alpha6Beta4Integrin;Laminin interactions;Collagen formation;Extracellular matrix organization;Anchoring fibril formation;Integrin;agrin in postsynaptic differentiation;Degradation of the extracellular matrix;a6b1 and a6b4 Integrin signaling;Non-integrin membrane-ECM interactions;MET activates PTK2 signaling;MET promotes cell motility;Signaling by MET;Type I hemidesmosome assembly;Cell junction organization;Signaling by Receptor Tyrosine Kinases;Cell-Cell communication;Beta1 integrin cell surface interactions;Alpha6 beta4 integrin-ligand interactions (Consensus)

Recessive Scores

• pRec: 0.327

Intolerance Scores

• loftool: 0.957
• rvis_EVS: 0.4
• rvis_percentile_EVS: 76.36

Haploinsufficiency Scores

• pHI: 0.103
• hipred: N
• hipred_score: 0.328
• ghis: 0.491

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.750

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Lamb3
• Phenotype: digestive/alimentary phenotype; skeleton phenotype; respiratory system 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); craniofacial phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype

Gene ontology

• Biological process: cell adhesion;epidermis development;extracellular matrix organization;hemidesmosome assembly;endodermal cell differentiation;brown fat cell differentiation
• Cellular component: extracellular region;laminin-5 complex
• Molecular function: structural molecule activity;protein binding;protein-containing complex binding