LAMA1

laminin subunit alpha 1, the group of Laminin subunits

Basic information

Region (hg38): 18:6941742-7117797

Previous symbols: [ "LAMA" ]

Links

ENSG00000101680NCBI:284217OMIM:150320HGNC:6481Uniprot:P25391AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

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

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Poretti-Boltshauser syndromeARGeneralGenetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testingNeurologic; Ophthalmologic25105227

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.

EffectPLPVUSLBBSum
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

GeneTypeBio TypeTranscript Coding Exons Length
LAMA1protein_codingprotein_codingENST00000389658 63176071
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
3.22e-321.0012550212451257480.000979
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-0.13617311.72e+31.010.00010420117
Missense in Polyphen611651.60.93777833
Synonymous-1.317356911.060.00004805924
Loss of Function5.54781520.5150.000007801902

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.001500.00149
Ashkenazi Jewish0.0003970.000397
East Asian0.001250.00125
Finnish0.0001900.000185
European (Non-Finnish)0.001290.00128
Middle Eastern0.001250.00125
South Asian0.0008210.000817
Other0.001310.00130

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

AllRecessiveDominant
MendelianHighHighHigh
Primary ImmunodeficiencyHighHighHigh
CancerHighHighHigh

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