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
laryngo-onycho-cutaneous syndrome (Definitive), 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 (1431 variants)
Inborn_genetic_diseases (483 variants)
Junctional_epidermolysis_bullosa_gravis_of_Herlitz (267 variants)
Laryngo-onycho-cutaneous_syndrome (172 variants)
Epidermolysis_bullosa,_junctional_2B,_severe (69 variants)
LAMA3-related_disorder (66 variants)
Epidermolysis_bullosa,_junctional_2A,_intermediate (62 variants)
Junctional_epidermolysis_bullosa (27 variants)
not_specified (22 variants)
Junctional_epidermolysis_bullosa,_non-Herlitz_type (9 variants)
Interstitial_lung_disease_2 (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. These statistics are base on transcript: NM_000198129.4. 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		1 clinvar	5 clinvar	682 clinvar	20 clinvar	708
missense	4 clinvar	6 clinvar	495 clinvar	94 clinvar	11 clinvar	610
nonsense	50 clinvar	21 clinvar	16 clinvar	1 clinvar		88
start loss						0
frameshift	49 clinvar	40 clinvar	15 clinvar			104
splice donor/acceptor (+/-2bp)	8 clinvar	72 clinvar	19 clinvar	1 clinvar		100
Total	111	140	550	778	31

Highest pathogenic variant AF is 0.000548976

Loading clinvar variants...

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