LAMA4

laminin subunit alpha 4, the group of Laminin subunits

Basic information

Region (hg38): 6:112107930-112254939

Links

ENSG00000112769 ∙ NCBI:3910 ∙ OMIM:600133 ∙ HGNC:6484 ∙ Uniprot:Q16363 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• dilated cardiomyopathy 1JJ (Limited), mode of inheritance: AD
• dilated cardiomyopathy 1JJ (Moderate), mode of inheritance: AD
• familial isolated dilated cardiomyopathy (Supportive), mode of inheritance: AD
• dilated cardiomyopathy 1JJ (Strong), mode of inheritance: AD
• dilated cardiomyopathy (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cardiomyopathy, dilated, 1JJ	AD	Cardiovascular	Individuals may have cardiovascular manifestations including dilated cardiomyopathy, and surveillance (eg, with echocardiogram) may allow detection and early medical treatment, which may be beneficial to help decrease morbidity; Heart transplantation was described as indicated in one individual	Cardiovascular	17646580
Although clinical effects have been described in older individuals, in at least one individual, the onset of cardiac pathology was such that surveillance may be indicated prior to adulthood

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LAMA4 gene.

• Dilated cardiomyopathy 1JJ (1021 variants)
• Cardiovascular phenotype (701 variants)
• not provided (475 variants)
• not specified (224 variants)
• Cardiomyopathy (73 variants)
• Inborn genetic diseases (27 variants)
• Primary dilated cardiomyopathy (8 variants)
• LAMA4-related condition (6 variants)
• Primary familial hypertrophic cardiomyopathy (6 variants)
• Arrhythmogenic right ventricular cardiomyopathy (3 variants)
• Hypertrophic cardiomyopathy;Ventricular tachycardia (1 variants)
• Brugada syndrome 9 (1 variants)
• Brugada syndrome (1 variants)
• Premature ventricular contraction (1 variants)
• Hypertrophic cardiomyopathy 1 (1 variants)
• Primary dilated cardiomyopathy;Long QT syndrome (1 variants)
• Catecholaminergic polymorphic ventricular tachycardia 1 (1 variants)
• Hypertrophic cardiomyopathy;Cardiomyopathy (1 variants)
• Spinocerebellar ataxia type 19/22 (1 variants)
• Familial atrial fibrillation (1 variants)
• Wolff-Parkinson-White pattern (1 variants)
• Dilated cardiomyopathy 3B (1 variants)
• Left ventricular noncompaction cardiomyopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LAMA4 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			5	302	9	316
missense		1	732	32	4	769
nonsense			16			16
start loss						0
frameshift			31			31
inframe indel			10			10
splice donor/acceptor (+/-2bp)			20			20
splice region			51	50	4	105
non coding			5	161	117	283
Total	0	1	819	495	130

Variants in LAMA4

This is a list of pathogenic ClinVar variants found in the LAMA4 region.

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

Position	Type	Phenotype	Significance	ClinVar
6-112109436-G-A		not specified • Cardiovascular phenotype • Cardiomyopathy	Conflicting classifications of pathogenicity (Jan 03, 2019)
6-112109440-G-A		Dilated cardiomyopathy 1JJ	Likely benign (Dec 07, 2020)
6-112109448-G-A		Cardiovascular phenotype	Uncertain significance (Feb 20, 2023)
6-112109449-A-G		Dilated cardiomyopathy 1JJ	Likely benign (Nov 05, 2019)
6-112109451-A-G		Dilated cardiomyopathy 1JJ • Cardiovascular phenotype	Uncertain significance (Dec 10, 2023)
6-112109453-G-A		Cardiovascular phenotype	Uncertain significance (Apr 17, 2023)
6-112109459-A-G		not specified • Cardiovascular phenotype • Dilated cardiomyopathy 1JJ • Cardiomyopathy • LAMA4-related disorder	Benign/Likely benign (Jan 25, 2024)
6-112109461-G-T		Cardiovascular phenotype	Uncertain significance (Jan 05, 2023)
6-112109464-T-TA		not specified • Dilated cardiomyopathy 1JJ • Cardiovascular phenotype	Conflicting classifications of pathogenicity (Jan 27, 2024)
6-112109464-T-TAC		Dilated cardiomyopathy 1JJ	Uncertain significance (Jul 08, 2023)
6-112109466-C-T		not specified • Dilated cardiomyopathy 1JJ • Cardiomyopathy	Benign/Likely benign (Jan 31, 2024)
6-112109467-G-A		not specified • Dilated cardiomyopathy 1JJ • Cardiovascular phenotype • LAMA4-related disorder	Likely benign (Jan 08, 2024)
6-112109469-C-A		Dilated cardiomyopathy 1JJ	Uncertain significance (Mar 17, 2022)
6-112109469-C-T		Dilated cardiomyopathy 1JJ • Cardiovascular phenotype	Uncertain significance (Nov 07, 2023)
6-112109470-G-A		Dilated cardiomyopathy 1JJ	Likely benign (Sep 14, 2023)
6-112109472-C-T		Dilated cardiomyopathy 1JJ • Cardiomyopathy	Uncertain significance (Sep 10, 2023)
6-112109490-T-C		Dilated cardiomyopathy 1JJ	Uncertain significance (Mar 08, 2023)
6-112109497-G-A		Dilated cardiomyopathy 1JJ • Cardiovascular phenotype	Likely benign (May 31, 2021)
6-112109504-G-T		Cardiovascular phenotype • Dilated cardiomyopathy 1JJ	Uncertain significance (Nov 01, 2023)
6-112109509-T-C		not specified • Dilated cardiomyopathy 1JJ • Cardiovascular phenotype	Likely benign (Jan 15, 2023)
6-112109511-C-T		Dilated cardiomyopathy 1JJ	Uncertain significance (Mar 10, 2021)
6-112109513-T-A		Cardiovascular phenotype	Uncertain significance (Sep 09, 2021)
6-112109516-A-C		Dilated cardiomyopathy 1JJ • Cardiovascular phenotype	Uncertain significance (May 19, 2021)
6-112109516-A-G		Cardiovascular phenotype • Dilated cardiomyopathy 1JJ • not specified	Conflicting classifications of pathogenicity (Jan 20, 2024)
6-112109525-T-G		Dilated cardiomyopathy 1JJ	Uncertain significance (Nov 27, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LAMA4	protein_coding	protein_coding	ENST00000230538	38	146179

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.39e-24	1.00	125583	0	165	125748	0.000656

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.148	968	981	0.987	0.0000544	12043
Missense in Polyphen		370	388.38	0.95267		4925
Synonymous	0.437	364	375	0.971	0.0000223	3449
Loss of Function	3.73	54	92.8	0.582	0.00000499	1132

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00119	0.00118
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.000927	0.000925
Finnish	0.00	0.00
European (Non-Finnish)	0.000611	0.000598
Middle Eastern	0.000927	0.000925
South Asian	0.00157	0.00157
Other	0.000653	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: Cardiomyopathy, dilated 1JJ (CMD1JJ) [MIM:615235]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. {ECO:0000269|PubMed:17646580}. 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);African trypanosomiasis - Homo sapiens (human);Amoebiasis - Homo sapiens (human);Toxoplasmosis - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);miRNA targets in ECM and membrane receptors;Focal Adhesion;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;Signal Transduction;prion pathway;Laminin interactions;Extracellular matrix organization;Beta3 integrin cell surface interactions;agrin in postsynaptic differentiation;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;FOXM1 transcription factor network (Consensus)

Recessive Scores

• pRec: 0.400

Intolerance Scores

• loftool: 0.405
• rvis_EVS: -1.33
• rvis_percentile_EVS: 4.68

Haploinsufficiency Scores

• pHI: 0.138
• hipred: N
• hipred_score: 0.492
• ghis: 0.531

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.639

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Lama4
• Phenotype: pigmentation 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; 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); liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); muscle 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; cellular phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: lama4
• Affected structure: somite border
• Phenotype tag: abnormal
• Phenotype quality: shape

Gene ontology

• Biological process: cell adhesion;regulation of cell adhesion;extracellular matrix organization;regulation of cell migration;regulation of embryonic development;negative regulation of cold-induced thermogenesis
• Cellular component: extracellular region;basement membrane;collagen-containing extracellular matrix;extracellular exosome
• Molecular function: signaling receptor binding;extracellular matrix structural constituent;protein binding