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 (34 variants)
• Ataxia - intellectual disability - oculomotor apraxia - cerebellar cysts syndrome (26 variants)
• LAMA1-related disorder (2 variants)
• Inborn genetic diseases (2 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.

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			4	260	40	304
missense		2	547	33	27	609
nonsense	23	11	1			35
start loss						0
frameshift	27	12				39
inframe indel		1	6			7
splice donor/acceptor (+/-2bp)	4	6	2			12
splice region	2	2	26	24	6	60
non coding	1		6	104	29	140
Total	55	32	566	397	96

Highest pathogenic variant AF is 0.0000986

Variants in LAMA1

This is a list of pathogenic ClinVar variants found in the LAMA1 region.

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

Position	Type	Phenotype	Significance	ClinVar
18-6942087-C-T			Uncertain significance (May 17, 2021)
18-6942109-GA-G		Ataxia - intellectual disability - oculomotor apraxia - cerebellar cysts syndrome	Likely pathogenic (Mar 12, 2018)
18-6942119-T-C		Inborn genetic diseases	Uncertain significance (Dec 13, 2023)
18-6942126-C-T			Uncertain significance (Aug 09, 2022)
18-6942130-C-T			Likely benign (Aug 15, 2022)
18-6942141-A-G			Uncertain significance (Aug 04, 2023)
18-6942147-A-G		Ataxia - intellectual disability - oculomotor apraxia - cerebellar cysts syndrome	Uncertain significance (May 06, 2021)
18-6942149-G-C			Uncertain significance (Dec 16, 2021)
18-6942161-G-A			Uncertain significance (Apr 06, 2022)
18-6942184-C-T			Likely benign (Mar 08, 2023)
18-6942196-G-A			Likely benign (May 04, 2023)
18-6942197-C-T			Uncertain significance (Oct 03, 2023)
18-6942202-C-T			Likely benign (May 03, 2022)
18-6942215-C-T			Uncertain significance (Jun 05, 2022)
18-6942216-G-A		Inborn genetic diseases	Uncertain significance (Dec 27, 2023)
18-6942239-G-T		Ataxia - intellectual disability - oculomotor apraxia - cerebellar cysts syndrome	Uncertain significance (Feb 06, 2020)
18-6943171-C-T			Uncertain significance (Mar 29, 2022)
18-6943172-G-A			Benign (Apr 29, 2023)
18-6943176-A-G		not specified • Inborn genetic diseases	Benign/Likely benign (Jan 08, 2024)
18-6943229-C-T			Benign (Dec 13, 2022)
18-6943249-C-T			Uncertain significance (Oct 03, 2023)
18-6943250-G-A			Likely benign (Nov 01, 2023)
18-6943251-C-T		Inborn genetic diseases	Uncertain significance (Jan 25, 2023)
18-6943256-T-C			Likely benign (Apr 01, 2023)
18-6943258-C-T		Inborn genetic diseases	Uncertain significance (Apr 16, 2024)

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