LAMA1

protein-coding

laminin subunit alpha 1, the group of Laminin subunits

Gene summary

This gene encodes one of the alpha 1 subunits of laminin. The laminins are a family of extracellular matrix glycoproteins that have a heterotrimeric structure consisting of an alpha, beta and gamma chain. These proteins make up a major component of the basement membrane and have been implicated in a wide variety of biological processes including cell adhesion, differentiation, migration, signaling, neurite outgrowth and metastasis. Mutations in this gene may be associated with Poretti-Boltshauser syndrome. [provided by RefSeq, Sep 2014]

Previous symbols:

LAMA

MANE transcript

NM_005559.4

Inheritance

ClinVar variants

P:160U:856B:547

Top phenotype

Poretti-Boltshauser syndrome

gnomAD constraint

pLI —, LoF o/e 0.51

Max pathogenic AF

—

Genomic locus

chr18:6,941,742-7,117,797

External References & Databases

Ensembl (ENSG00000101680)

Transcript & Mutation Effects

hg38 • Region Span ~176.1 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

ataxia - intellectual disability - oculomotor apraxia - cerebellar cysts syndromeDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014419

Submitter: G2P

ataxia - intellectual disability - oculomotor apraxia - cerebellar cysts syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014419

Submitter: Labcorp Genetics (formerly Invitae)

ataxia - intellectual disability - oculomotor apraxia - cerebellar cysts syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014419

Submitter: PanelApp Australia

ataxia - intellectual disability - oculomotor apraxia - cerebellar cysts syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014419

Submitter: Orphanet

Clinical Genomic Database (CGD)

Poretti-Boltshauser syndromeAR

Manifestation: Neurologic; Ophthalmologic

Intervention: General

Rationale: 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

Refs: 25105227

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to LAMA1 variants in ClinVar

12 Conditions Cataloged

not providedTotal: 1245

Inborn genetic diseasesTotal: 505

not specifiedTotal: 439

Ataxia - intellectual disability - oculomotor apraxia - cerebellar cysts syndromeTotal: 182

LAMA1-related disorderTotal: 133

Retinal dystrophyTotal: 18

Optic atrophyTotal: 3

Intellectual disabilityTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005559.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous		1 clinvar	10 clinvar	403 clinvar	20 clinvar	434
missense		4 clinvar	833 clinvar	109 clinvar	15 clinvar	961
nonsense	24 clinvar	29 clinvar	2 clinvar			55
start loss						0
frameshift	38 clinvar	41 clinvar				79
splice donor/acceptor (+/-2bp)	3 clinvar	20 clinvar	11 clinvar			34
Total	65	95	856	512	35	1563

Highest pathogenic variant AF is 0.00019877875

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 11 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005559.4	RefSeq	NP_005550.2	63	MANE Select
ENST00000389658.4	Ensembl	ENSP00000374309.3	63	MANE Select
ENST00000940200.1	Ensembl	ENSP00000610259.1	63	Standard
ENST00000940200.2	Ensembl	ENSP00000610259.1	63	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
lama1	Danio rerio	Structure: retinal ganglion cell Quality: poorly differentiated abnormal

Gene / Model

Organism

Observed Phenotype

lama1

Danio rerio

Structure: retinal ganglion cell

Quality: poorly differentiated

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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)

Biological Process

morphogenesis of an epithelial sheet
protein phosphorylation
cell adhesion
cell surface receptor signaling pathway
regulation of cell adhesion

Molecular Function

signaling receptor binding
extracellular matrix structural constituent
protein binding
protein C-terminus binding
glycosphingolipid binding

Cellular Component

extracellular region
basement membrane
laminin-1 complex
laminin-3 complex
extracellular space

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000389658
Coding exons: 63
Length: 176071
Individuals with no LoFs: 125502
Homozygous LoFs: 1
Heterozygous LoFs: 245
Defined: 125748
p: 0.000979

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.136	1731	1.72e+3	1.01	0.000104	20117
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00081	0.00080	rare
Latino/Admixed American	0.00069	0.00069	rare
Ashkenazi Jewish	0.00040	0.00040	rare
East Asian	0.0013	0.0013	notable
Finnish	0.00019	0.00018	rare
European (Non-Finnish)	0.0013	0.0013	notable
South Asian	0.00082	0.00082	rare
Other	0.0013	0.0013	notable

dbNSFP Gene Annotations

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.;

Intolerance Scores

LoFtool: 0.876
RVIS EVS: 0.73
RVIS percentile EVS: 86.22

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.551

Gene Damage Prediction

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