LAMA3

laminin subunit alpha 3, the group of Laminin subunits

Basic information

Region (hg38): 18:23689453-23956222

Previous symbols: [ "LAMNA" ]

Links

ENSG00000053747 ∙ NCBI:3909 ∙ OMIM:600805 ∙ HGNC:6483 ∙ Uniprot:Q16787 ∙ 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
• laryngo-onycho-cutaneous syndrome (Strong), mode of inheritance: AR
• junctional epidermolysis bullosa, non-Herlitz type (Strong), mode of inheritance: AR
• junctional epidermolysis bullosa Herlitz type (Strong), mode of inheritance: AR
• laryngo-onycho-cutaneous syndrome (Supportive), 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
• junctional epidermolysis bullosa Herlitz type (Strong), mode of inheritance: AR
• laryngo-onycho-cutaneous syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Epidermolysis bullosa, junctional 2A, intermediate; Epidermolysis bullosa, junctional 2B, severe; Epidermolysis bullosa, junctional 2C, laryngoonychocutaneous	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	Audiologic/Otolaryngologic; Dental; Dermatologic	1342856; 8185366; 7633458; 8530087; 8618022; 8586427; 11810295; 12915477; 20301304; 20881434; 22434185; 22963541
The condition can include life-threatening respiratory obstruction

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LAMA3 gene.

• not provided (97 variants)
• Junctional epidermolysis bullosa (7 variants)
• Junctional epidermolysis bullosa gravis of Herlitz (6 variants)
• Epidermolysis bullosa, junctional 2B, severe (3 variants)
• Laryngo-onycho-cutaneous syndrome (2 variants)
• Laryngo-onycho-cutaneous syndrome;Epidermolysis bullosa, junctional 2B, severe;Epidermolysis bullosa, junctional 2A, intermediate (1 variants)
• Junctional epidermolysis bullosa gravis of Herlitz;Epidermolysis bullosa, junctional 2A, intermediate;Epidermolysis bullosa, junctional 2B, severe;Laryngo-onycho-cutaneous syndrome (1 variants)
• Junctional epidermolysis bullosa, non-Herlitz type (1 variants)
• Epidermolysis bullosa, junctional 2A, intermediate (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LAMA3 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			4	658	25	687
missense	3	2	280	48	13	346
nonsense	46	21	16			83
start loss		2				2
frameshift	48	34	15			97
inframe indel			6			6
splice donor/acceptor (+/-2bp)	8	60	19	1		88
splice region			5	96	6	107
non coding	1	1	9	271	95	377
Total	106	120	349	978	133

Highest pathogenic variant AF is 0.000210

Variants in LAMA3

This is a list of pathogenic ClinVar variants found in the LAMA3 region.

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

Position	Type	Phenotype	Significance	ClinVar
18-23689699-CG-C		Junctional epidermolysis bullosa gravis of Herlitz	Uncertain significance (Apr 24, 2017)
18-23689709-G-A		Inborn genetic diseases	Uncertain significance (Jun 11, 2024)
18-23689736-C-G		Inborn genetic diseases	Uncertain significance (Apr 23, 2024)
18-23689740-G-C			Benign (Sep 12, 2022)
18-23689762-C-A			Benign/Likely benign (Jul 05, 2022)
18-23689765-G-A		Inborn genetic diseases • LAMA3-related disorder	Uncertain significance (Feb 21, 2023)
18-23689780-G-C		Inborn genetic diseases	Uncertain significance (Feb 15, 2023)
18-23689803-G-A		LAMA3-related disorder	Likely benign (Sep 26, 2022)
18-23689813-G-C		Inborn genetic diseases	Likely benign (Oct 03, 2022)
18-23689830-G-A			Likely benign (Mar 01, 2022)
18-23689843-C-T		LAMA3-related disorder	Likely benign (Jan 31, 2020)
18-23689895-C-T		Inborn genetic diseases	Uncertain significance (Jun 29, 2022)
18-23689909-C-A		Inborn genetic diseases	Uncertain significance (Aug 02, 2022)
18-23689936-G-A		Inborn genetic diseases	Uncertain significance (Feb 05, 2024)
18-23689950-C-T			Benign (Jul 24, 2020)
18-23689960-A-G		Inborn genetic diseases	Uncertain significance (Jul 30, 2023)
18-23690024-G-T			Benign (May 13, 2021)
18-23690207-A-C			Benign (Jun 19, 2021)
18-23713937-T-C			Benign (Aug 21, 2023)
18-23713960-A-G		Inborn genetic diseases	Uncertain significance (Nov 09, 2021)
18-23713990-G-A		Inborn genetic diseases	Uncertain significance (Jun 22, 2021)
18-23713999-G-A		Inborn genetic diseases	Uncertain significance (Jan 03, 2024)
18-23714014-C-G		Inborn genetic diseases	Uncertain significance (May 06, 2022)
18-23714015-TC-T		Junctional epidermolysis bullosa gravis of Herlitz	Uncertain significance (Oct 18, 2017)
18-23714041-A-G		Inborn genetic diseases	Uncertain significance (Apr 17, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LAMA3	protein_coding	protein_coding	ENST00000313654	75	265624

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.83e-46	1.00	125397	0	351	125748	0.00140

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.487	1752	1.81e+3	0.968	0.000108	21794
Missense in Polyphen		531	588.73	0.90194		7306
Synonymous	0.368	680	692	0.982	0.0000425	6494
Loss of Function	5.05	102	174	0.586	0.00000946	2130

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00277	0.00265
Ashkenazi Jewish	0.0000994	0.0000992
East Asian	0.00550	0.00540
Finnish	0.000139	0.000139
European (Non-Finnish)	0.00122	0.00118
Middle Eastern	0.00550	0.00540
South Asian	0.00147	0.00147
Other	0.000658	0.000652

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:7633458, ECO:0000269|PubMed:8530087}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Laryngoonychocutaneous syndrome (LOCS) [MIM:245660]: Autosomal recessive epithelial disorder confined to the Punjabi Muslim population. The condition is characterized by cutaneous erosions, nail dystrophy and exuberant vascular granulation tissue in certain epithelia, especially conjunctiva and larynx. {ECO:0000269|PubMed:12915477}. 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;Overview of nanoparticle effects;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;agrin in postsynaptic differentiation;Degradation of the extracellular matrix;a6b1 and a6b4 Integrin signaling;Non-integrin membrane-ECM interactions;ECM proteoglycans;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;Validated transcriptional targets of AP1 family members Fra1 and Fra2;Syndecan-4-mediated signaling events;Syndecan-2-mediated signaling events (Consensus)

Recessive Scores

• pRec: 0.403

Intolerance Scores

• loftool: 0.948
• rvis_EVS: -2.06
• rvis_percentile_EVS: 1.63

Haploinsufficiency Scores

• pHI: 0.103
• hipred: Y
• hipred_score: 0.600
• ghis: 0.529

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.698

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Lama3
• 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; craniofacial phenotype; homeostasis/metabolism 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); hematopoietic system phenotype; digestive/alimentary phenotype; immune system phenotype

Gene ontology

• Biological process: cell adhesion;epidermis development;regulation of cell adhesion;extracellular matrix organization;regulation of cell migration;hemidesmosome assembly;endodermal cell differentiation;regulation of embryonic development
• Cellular component: extracellular region;basement membrane;laminin-5 complex;endoplasmic reticulum;collagen-containing extracellular matrix;extracellular exosome
• Molecular function: signaling receptor binding;structural molecule activity;extracellular matrix structural constituent