GeneBe

LAMB3

protein-coding

laminin subunit beta 3, the group of Laminin subunits|MicroRNA protein coding host genes

Gene summary

The product encoded by this gene is a laminin that belongs to a family of basement membrane proteins. This protein is a beta subunit laminin, which together with an alpha and a gamma subunit, forms laminin-5. Mutations in this gene cause epidermolysis bullosa junctional Herlitz type, and generalized atrophic benign epidermolysis bullosa, diseases that are characterized by blistering of the skin. Multiple alternatively spliced transcript variants that encode the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

Previous symbols:
  • LAMNB1

MANE transcript

NM_000228.3

Inheritance

AR, AD, SD

ClinVar variants

P:365U:360B:545

Top phenotype

Epidermolysis bullosa, junctional 1B, severe

gnomAD constraint

pLI —, LoF o/e 0.55

Max pathogenic AF

—

Genomic locus

chr1:209,614,870-209,652,425

External References & Databases

Ensembl (ENSG00000196878)NCBI Gene (3914)OMIM (150310)HGNC:6490GenCCUniProt (Q13751)AlphaFoldClinVar (LAMB3)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~37.6 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

junctional epidermolysis bullosaDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0017612

Submitter: Myriad Women's Health

junctional epidermolysis bullosa Herlitz typeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009182

Submitter: Genomics England PanelApp

amelogenesis imperfecta type 1AMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0007094

Submitter: Ambry Genetics

junctional epidermolysis bullosa, non-Herlitz typeDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009180

Submitter: Ambry Genetics

junctional epidermolysis bullosa Herlitz typeDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009182

Submitter: Ambry Genetics

amelogenesis imperfecta type 1SUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0015047

Submitter: Orphanet

generalized junctional epidermolysis bullosa non-Herlitz typeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0019307

Submitter: Orphanet

junctional epidermolysis bullosa Herlitz typeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009182

Submitter: Orphanet

junctional epidermolysis bullosa, non-Herlitz typeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009180

Submitter: Genomics England PanelApp

amelogenesis imperfecta type 1ASTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0007094

Submitter: Labcorp Genetics (formerly Invitae)

junctional epidermolysis bullosa Herlitz typeDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009182

Submitter: Laboratory for Molecular Medicine

This gene-disease relationship has undergone rapid assessment. Classifications are based on preliminary review of gene-disease validity during analysis of genomic sequencing results.

junctional epidermolysis bullosa Herlitz typeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009182

Submitter: Labcorp Genetics (formerly Invitae)

amelogenesis imperfecta type 1ASTRONG

Inheritance Pattern: SD

Disease ID:MONDO:0007094

Submitter: PanelApp Australia

junctional epidermolysis bullosa Herlitz typeSTRONG

Inheritance Pattern: SD

Disease ID:MONDO:0009182

Submitter: PanelApp Australia

junctional epidermolysis bullosa, non-Herlitz typeSTRONG

Inheritance Pattern: SD

Disease ID:MONDO:0009180

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Epidermolysis bullosa, junctional 1B, severeAR

Manifestation: Dental; Dermatologic

Intervention: Dermatologic

Rationale: Epidermolysis bullosa, junctional 1B, severe involves a severe and sometimes fatal blistering skin disease, and treatment with autologous transgenic keratinocyte cultures has been described as beneficial

Refs: 7706760; 7774918; 9205497; 9242513; 11023379; 15538630; 16473856; 17476356; 20301304; 19369679; 20301304; 21801158; 23632796; 23958762; 29144448Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to LAMB3 variants in ClinVar

13 Conditions Cataloged
not providedTotal: 1068
Inborn genetic diseasesTotal: 277
Junctional epidermolysis bullosaTotal: 246
Junctional epidermolysis bullosa gravis of HerlitzTotal: 171
Junctional epidermolysis bullosa, non-Herlitz typeTotal: 89
Amelogenesis imperfecta type 1ATotal: 77
LAMB3-related disorderTotal: 76
not specifiedTotal: 66

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000228.3. 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.

EffectPLPVUSLBBSum
synonymous
1
clinvar
4
clinvar
491
clinvar
2
clinvar
 498
missense
2
clinvar
7
clinvar
350
clinvar
46
clinvar
6
clinvar
 411
nonsense
65
clinvar
53
clinvar
1
clinvar
 119
start loss
2
clinvar
 2
frameshift
107
clinvar
62
clinvar
 169
splice donor/acceptor (+/-2bp)
12
clinvar
54
clinvar
5
clinvar
 71
Total18617936053781270

Highest pathogenic variant AF is 0.0006833953

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 36 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_000228.3RefSeqNP_000219.222MANE Select
ENST00000356082.9EnsemblENSP00000348384.322MANE Select
NM_001017402.2RefSeqNP_001017402.122Standard
NM_001127641.1RefSeqNP_001121113.122Standard

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

  • cell adhesion
  • epidermis development
  • extracellular matrix organization
  • hemidesmosome assembly
  • endodermal cell differentiation

Molecular Function

  • structural molecule activity
  • protein binding
  • protein-containing complex binding

Cellular Component

  • extracellular region
  • laminin-5 complex

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000391911
Coding exons
22
Length
37597
Individuals with no LoFs
125441
Homozygous LoFs
0
Heterozygous LoFs
307
Defined
125748
p
0.00122
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-0.5257477081.060.00004857596
Missense (PolyPhen)197203.930.966032214
Synonymous-0.9522972771.070.00001802356
Loss of Function3.243461.40.5540.00000345655

Population LoF Frequency

PopulationCAFp-valueStatus
African0.00140.0014notable
Latino/Admixed American0.000460.00046rare
Ashkenazi Jewish0.000400.00040rare
East Asian0.000490.00049rare
Finnish0.000460.00046rare
European (Non-Finnish)0.00190.0019notable
South Asian0.000830.00082rare
Other0.000490.00049rare

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: Epidermolysis bullosa, junctional, Herlitz type (H-JEB) [MIM:226700]: An infantile and lethal form of junctional epidermolysis bullosa, a group of blistering skin diseases characterized by tissue separation which occurs within the dermo- epidermal basement In the Herlitz type, death occurs usually within the first six months of life. Occasionally, children survive to teens. It is marked by bullous lesions at birth and extensive denudation of skin and mucous membranes that may be hemorrhagic. {ECO:0000269|PubMed:7550237}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Generalized atrophic benign epidermolysis bullosa (GABEB) [MIM:226650]: A non-lethal, adult form of junctional epidermolysis bullosa characterized by life-long blistering of the skin, associated with hair and tooth abnormalities. {ECO:0000269|PubMed:17476356, ECO:0000269|PubMed:9767254}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Amelogenesis imperfecta 1A (AI1A) [MIM:104530]: A form of amelogenesis imperfecta, a disorder characterized by defective enamel formation. The enamel may be hypoplastic, hypomineralized or both, and affected teeth may be discoloured, sensitive or prone to disintegration. {ECO:0000269|PubMed:23632796, ECO:0000269|PubMed:23958762}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.327

Intolerance Scores

LoFtool
0.957
RVIS EVS
0.4
RVIS percentile EVS
76.36

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.750

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumHigh
CancerMediumMediumMedium
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