LAMA1

laminin subunit alpha 1, the group of Laminin subunits

Basic information

Region (hg38): 18:6941742-7117797

Previous symbols: [ "LAMA" ]

Links

ENSG00000101680

∙ NCBI:284217 ∙ OMIM:150320 ∙ HGNC:6481 ∙ Uniprot:P25391 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

ataxia - intellectual disability - oculomotor apraxia - cerebellar cysts syndrome (Definitive), mode of inheritance: AR
ataxia - intellectual disability - oculomotor apraxia - cerebellar cysts syndrome (Strong), mode of inheritance: AR
ataxia - intellectual disability - oculomotor apraxia - cerebellar cysts syndrome (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Poretti-Boltshauser syndrome	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	Neurologic; Ophthalmologic	25105227

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LAMA1 gene.

not_provided (1104 variants)
Inborn_genetic_diseases (448 variants)
Ataxia_-_intellectual_disability_-_oculomotor_apraxia_-_cerebellar_cysts_syndrome (152 variants)
LAMA1-related_disorder (66 variants)
not_specified (55 variants)
Retinal_dystrophy (18 variants)
Optic_atrophy (3 variants)
Intellectual_disability (3 variants)
EBV-positive_nodal_T-_and_NK-cell_lymphoma (1 variants)
See_cases (1 variants)
Muscular_dystrophy,_congenital,_merosin_deficient_or_partially_deficient (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LAMA1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000005559.4. 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	8 clinvar	301 clinvar	28 clinvar	338
missense	2 clinvar	4 clinvar	749 clinvar	77 clinvar	18 clinvar	850
nonsense	26 clinvar	16 clinvar	2 clinvar			44
start loss						0
frameshift	33 clinvar	17 clinvar				50
splice donor/acceptor (+/-2bp)	3 clinvar	12 clinvar	2 clinvar			17
Total	64	50	761	378	46

Highest pathogenic variant AF is 0.00019877875

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LAMA1	protein_coding	protein_coding	ENST00000389658	63	176071

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.22e-32	1.00	125502	1	245	125748	0.000979

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.136	1731	1.72e+3	1.01	0.000104	20117
Missense in Polyphen		611	651.6	0.9377		7833
Synonymous	-1.31	735	691	1.06	0.0000480	5924
Loss of Function	5.54	78	152	0.515	0.00000780	1902

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00150	0.00149
Ashkenazi Jewish	0.000397	0.000397
East Asian	0.00125	0.00125
Finnish	0.000190	0.000185
European (Non-Finnish)	0.00129	0.00128
Middle Eastern	0.00125	0.00125
South Asian	0.000821	0.000817
Other	0.00131	0.00130

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: Poretti-Boltshauser syndrome (PTBHS) [MIM:615960]: An autosomal recessive disorder characterized by cerebellar dysplasia, cerebellar vermis atrophy, cerebellar cysts in most patients, high myopia, variable retinal dystrophy, and eye movement abnormalities including strabismus, ocular apraxia, nystagmus. Affected individuals have ataxia, delayed motor development, language impairment, and intellectual disability with variable severity. {ECO:0000269|PubMed:25105227}. 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;Developmental Biology;Signal Transduction;prion pathway;Laminin interactions;Extracellular matrix organization;agrin in postsynaptic differentiation;a6b1 and a6b4 Integrin signaling;L1CAM interactions;Non-integrin membrane-ECM interactions;Axon guidance;ECM proteoglycans;MET activates PTK2 signaling;MET promotes cell motility;Signaling by MET;Signaling by Receptor Tyrosine Kinases;Glypican 1 network;Beta1 integrin cell surface interactions;Alpha6 beta4 integrin-ligand interactions;Syndecan-4-mediated signaling events;Syndecan-2-mediated signaling events (Consensus)

Intolerance Scores

loftool: 0.876
rvis_EVS: 0.73
rvis_percentile_EVS: 86.22

Haploinsufficiency Scores

pHI: 0.174
hipred: Y
hipred_score: 0.577
ghis: 0.461

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.551

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Lama1
Phenotype: embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); 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); normal 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); vision/eye phenotype; growth/size/body region phenotype; cellular phenotype;

Zebrafish Information Network

Gene name: lama1
Affected structure: retinal ganglion cell
Phenotype tag: abnormal
Phenotype quality: poorly differentiated

Gene ontology

Biological process: morphogenesis of an epithelial sheet;protein phosphorylation;cell adhesion;cell surface receptor signaling pathway;regulation of cell adhesion;extracellular matrix organization;regulation of cell migration;neuron projection development;establishment of epithelial cell apical/basal polarity;regulation of embryonic development;epithelial tube branching involved in lung morphogenesis;branching involved in salivary gland morphogenesis;retinal blood vessel morphogenesis
Cellular component: extracellular region;basement membrane;laminin-1 complex;laminin-3 complex;extracellular space;cell-cell junction;membrane;extracellular matrix;collagen-containing extracellular matrix
Molecular function: signaling receptor binding;extracellular matrix structural constituent;protein binding;protein C-terminus binding;glycosphingolipid binding