LAMA5

laminin subunit alpha 5, the group of Laminin subunits|MicroRNA protein coding host genes

Basic information

Region (hg38): 20:62307954-62367312

Links

ENSG00000130702 ∙ NCBI:3911 ∙ OMIM:601033 ∙ HGNC:6485 ∙ Uniprot:O15230 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• LAMA5-related multisystemic syndrome (Supportive), mode of inheritance: AD
• nephrotic syndrome, IIa 26 (Moderate), mode of inheritance: AR
• nephrotic syndrome, IIa 26 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Bent bone dysplasia syndrome 2	AR	Cardiovascular	Among other features, the condition can include atrial septal defects, and awareness may allow early diagnosis and management	Cardiovascular; Craniofacial; Musculoskeletal; Renal	29534211; 33242826; 35419533
Some individuals with Nephrotic syndrome, type 26 have been reported as being responsive to steroids

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LAMA5 gene.

• not provided (1040 variants)
• Inborn genetic diseases (262 variants)
• LAMA5-related condition (36 variants)
• Nephrotic syndrome (11 variants)
• Nephrotic syndrome, IIa 26 (7 variants)
• not specified (6 variants)
• Short stature (4 variants)
• Presynaptic congenital myasthenic syndrome (3 variants)
• Bent bone dysplasia syndrome 2 (2 variants)
• Polymicrogyria (2 variants)
• distinct bent bone dysplasia (2 variants)
• Severe hydrocephalus;Holoprosencephaly sequence (2 variants)
• Developmental disorder (1 variants)
• Congenital omphalocele (1 variants)
• Malignant tumor of prostate (1 variants)
• Macroscopic hematuria (1 variants)
• Familial hematuria (1 variants)
• High myopia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LAMA5 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			12	225	78	315
missense		6	506	63	84	659
nonsense		2	3			5
start loss						0
frameshift		3	1			4
inframe indel			3		1	4
splice donor/acceptor (+/-2bp)			2			2
splice region			14	27	18	59
non coding			4	78	122	204
Total	0	11	531	366	285

Highest pathogenic variant AF is 0.0000723

Variants in LAMA5

This is a list of pathogenic ClinVar variants found in the LAMA5 region.

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

Position	Type	Phenotype	Significance	ClinVar
20-62308045-C-T		not specified	Uncertain significance (May 08, 2023)
20-62308109-A-G			Benign (Jul 20, 2018)
20-62308134-G-A		not specified	Uncertain significance (Nov 27, 2023)
20-62308135-C-T			Benign (Jul 31, 2018)
20-62308711-G-A		not specified	Uncertain significance (Dec 03, 2021)
20-62308736-A-G		not specified	Uncertain significance (Nov 07, 2022)
20-62308747-A-G		not specified	Uncertain significance (Jun 29, 2022)
20-62309283-G-A			Benign (May 14, 2021)
20-62309336-C-A			Uncertain significance (May 31, 2023)
20-62309342-G-A			Likely benign (Aug 01, 2023)
20-62309346-G-A		LAMA5-related disorder	Likely benign (Sep 17, 2023)
20-62309356-T-C		Inborn genetic diseases	Uncertain significance (May 27, 2022)
20-62309357-G-A		LAMA5-related disorder	Benign (Jan 25, 2024)
20-62309371-C-T		not specified • LAMA5-related disorder	Benign/Likely benign (Mar 01, 2024)
20-62309378-C-T		LAMA5-related disorder	Likely benign (Jul 27, 2023)
20-62309383-C-G			Uncertain significance (May 08, 2020)
20-62309391-G-C		LAMA5-related disorder	Uncertain significance (May 17, 2023)
20-62309395-T-C			Uncertain significance (May 08, 2023)
20-62309398-C-T		Inborn genetic diseases	Likely benign (Mar 13, 2023)
20-62309399-G-A		LAMA5-related disorder	Likely benign (May 13, 2021)
20-62309410-G-A		Inborn genetic diseases	Conflicting classifications of pathogenicity (Oct 13, 2023)
20-62309415-A-G		Inborn genetic diseases	Uncertain significance (Dec 19, 2022)
20-62309417-C-T		LAMA5-related disorder	Benign (Jan 25, 2024)
20-62309427-C-T			Benign (Jan 08, 2024)
20-62309438-G-A		LAMA5-related disorder	Likely benign (May 27, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LAMA5	protein_coding	protein_coding	ENST00000252999	80	59358

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00647	0.994	125353	0	149	125502	0.000594

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.272	2301	2.26e+3	1.02	0.000165	23392
Missense in Polyphen		499	570.18	0.87516		5807
Synonymous	-6.45	1240	983	1.26	0.0000750	7679
Loss of Function	9.48	44	182	0.242	0.00000988	1948

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00112	0.00109
Ashkenazi Jewish	0.000640	0.000597
East Asian	0.000783	0.000762
Finnish	0.000343	0.000323
European (Non-Finnish)	0.000729	0.000662
Middle Eastern	0.000783	0.000762
South Asian	0.000663	0.000621
Other	0.000697	0.000653

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.
• 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;Primary Focal Segmental Glomerulosclerosis FSGS;Human Complement System;Focal Adhesion;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;Interleukin-4 and 13 signaling;PI3K-Akt Signaling Pathway;Inflammatory Response Pathway;Signal Transduction;prion pathway;Alpha6Beta4Integrin;Laminin interactions;Extracellular matrix organization;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;Signaling by Receptor Tyrosine Kinases;Beta1 integrin cell surface interactions;Syndecan-1-mediated signaling events;Alpha6 beta4 integrin-ligand interactions (Consensus)

Intolerance Scores

• loftool: 0.482
• rvis_EVS: 3.13
• rvis_percentile_EVS: 99.28

Haploinsufficiency Scores

• pHI: 0.710
• hipred: Y
• hipred_score: 0.683
• ghis: 0.483

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.959

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Lama5
• Phenotype: vision/eye phenotype; digestive/alimentary phenotype; hearing/vestibular/ear 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); limbs/digits/tail phenotype; skeleton phenotype; renal/urinary system phenotype; immune system phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; growth/size/body region 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; homeostasis/metabolism phenotype; cellular phenotype; endocrine/exocrine gland phenotype

Zebrafish Information Network

• Gene name: lama5
• Affected structure: epidermal cell
• Phenotype tag: abnormal
• Phenotype quality: shape

Gene ontology

• Biological process: angiogenesis;branching involved in ureteric bud morphogenesis;morphogenesis of a polarized epithelium;neural crest cell migration;hair follicle development;cytoskeleton organization;integrin-mediated signaling pathway;muscle organ development;cell recognition;cell population proliferation;morphogenesis of embryonic epithelium;cell migration;cytokine-mediated signaling pathway;cell differentiation;regulation of cell adhesion;extracellular matrix organization;lung development;regulation of cell migration;substrate adhesion-dependent cell spreading;regulation of cell population proliferation;odontogenesis of dentin-containing tooth;endothelial cell differentiation;regulation of embryonic development;focal adhesion assembly;cilium assembly;branching involved in salivary gland morphogenesis;protein localization to plasma membrane
• Cellular component: extracellular region;basement membrane;laminin-5 complex;extracellular space;nucleus;neuromuscular junction;synaptic cleft;laminin-10 complex;laminin-11 complex;collagen-containing extracellular matrix;extracellular exosome
• Molecular function: integrin binding;extracellular matrix structural constituent