LAMA4 laminin subunit alpha 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: LAMA4provided by HGNC
Official Full Name: laminin subunit alpha 4provided by HGNC
Primary source: HGNC:HGNC:6484
See related: Ensembl:ENSG00000112769 MIM:600133; AllianceGenome:HGNC:6484
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: LAMA3; CMD1JJ; LAMA4*-1
Summary: Laminins, a family of extracellular matrix glycoproteins, are the major noncollagenous constituent of basement membranes. They have been implicated in a wide variety of biological processes including cell adhesion, differentiation, migration, signaling, neurite outgrowth and metastasis. Laminins are composed of 3 non identical chains: laminin alpha, beta and gamma (formerly A, B1, and B2, respectively) and they form a cruciform structure consisting of 3 short arms, each formed by a different chain, and a long arm composed of all 3 chains. Each laminin chain is a multidomain protein encoded by a distinct gene. Several isoforms of each chain have been described. Different alpha, beta and gamma chain isomers combine to give rise to different heterotrimeric laminin isoforms which are designated by Arabic numerals in the order of their discovery, i.e. alpha1beta1gamma1 heterotrimer is laminin 1. The biological functions of the different chains and trimer molecules are largely unknown, but some of the chains have been shown to differ with respect to their tissue distribution, presumably reflecting diverse functions in vivo. This gene encodes the alpha chain isoform laminin, alpha 4. The domain structure of alpha 4 is similar to that of alpha 3, both of which resemble truncated versions of alpha 1 and alpha 2, in that approximately 1,200 residues at the N-terminus (domains IV, V and VI) have been lost. Laminin, alpha 4 contains the C-terminal G domain which distinguishes all alpha chains from the beta and gamma chains. The RNA analysis from adult and fetal tissues revealed developmental regulation of expression, however, the exact function of laminin, alpha 4 is not known. Tissue-specific utilization of alternative polyA-signal has been described in literature. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Aug 2011]
Expression: Broad expression in fat (RPKM 48.0), endometrium (RPKM 32.2) and 20 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 6q21

Exon count:: 41

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	6	NC_000006.12 (112107931..112254985, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	6	NC_060930.1 (113291349..113438419, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (112429134..112575769, complement)

Chromosome 6 - NC_000006.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

[Research Progress on the Role of Laminin Subunit Alpha 4 in Diseases].
Title: [Research Progress on the Role of Laminin Subunit Alpha 4 in Diseases].
Laminin-alpha4 Is Upregulated in Both Human and Murine Models of Obesity.
Title: Laminin-α4 Is Upregulated in Both Human and Murine Models of Obesity.
Effect of LAMA4 on Prognosis and Its Correlation with Immune Infiltration in Gastric Cancer.
Title: Effect of LAMA4 on Prognosis and Its Correlation with Immune Infiltration in Gastric Cancer.
Laminin Subunit Alpha-4 and Osteopontin Are Glioblastoma-Selective Secreted Proteins That Are Increased in the Cerebrospinal Fluid of Glioblastoma Patients.
Title: Laminin Subunit Alpha-4 and Osteopontin Are Glioblastoma-Selective Secreted Proteins That Are Increased in the Cerebrospinal Fluid of Glioblastoma Patients.
In diverse models, laminins alpha-4 (LAMA4) and alpha-5 (LAMA5) were differentially regulated. Immunity was associated with decreased LAMA4:LAMA5 ratio, while tolerance was associated with an increased ratio. LAMA4inhibited CD4+ T-cell proliferation and Th1, Th2, and Th17 polarization but favored Treg induction. LAMA4 and LAMA5 are coinhibitory and costimulatory ligands for human and mouse CD4 T cells, respectively.
Title: Differential Regulation of T-cell Immunity and Tolerance by Stromal Laminin Expressed in the Lymph Node.
Downregulation of the LAMA4 gene inhibits the proliferation, migration, and invasion of extravillous trophoblasts to suppress the expression of vascular factors, leading to the occurrence or development of preeclampsia.
Title: Role of LAMA4 Gene in Regulating Extravillous Trophoblasts in Pathogenesis of Preeclampsia.
High LAMA4 expression is associated with inflammation in asthma.
Title: Laminin α4 contributes to airway remodeling and inflammation in asthma.
High LAMA4 expression is associated with gastric cancer.
Title: LAMA4 expression is activated by zinc finger E‑box‑binding homeobox 1 and independently predicts poor overall survival in gastric cancer.
Disruption of LAMA4, LAMA5, and LAMB2 or the laminin-receptor interaction occurs in neuromuscular diseases including Pierson syndrome and Lambert-Eaton myasthenic syndrome (LEMS). (Review)
Title: The role of laminins in the organization and function of neuromuscular junctions.
highlight MCAM and LAMA4 as prime candidates for RCC prognosis and therapeutic targeting
Title: MCAM and LAMA4 Are Highly Enriched in Tumor Blood Vessels of Renal Cell Carcinoma and Predict Patient Outcome.

Submit: New GeneRIF Correction See all GeneRIFs (31)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Dilated cardiomyopathy 1JJ MedGen: C3808935 OMIM: 615235 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120 inhibits CD3-triggered T cell co-stimulation by the extracellular matrix (ECM) proteins, which includes laminins	PubMed
Envelope transmembrane glycoprotein gp41	env	HIV-1 gp41 inhibits CD3-triggered T cell co-stimulation by the extracellular matrix (ECM) proteins, which includes laminins	PubMed
Tat	tat	Treatment with cannabinoids inhibits HIV-1 Tat-enhanced attachment of U937 cells to collagen IV, laminin, or ECM1 proteins, which is linked to the cannabinoid receptor type 2 and the modulation of beta1-integrin and actin distribution	PubMed
	tat	HIV-1 Tat enhances adhesion of human U937 monocyte-like cells to proteins of the extracellular matrix, such as collagen IV, laminin, and ECM1	PubMed
	tat	HIV-1 Tat upregulates the expression of extracellular matrix proteins, including the major basement membrane protein laminin	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

WI-18524 (e-PCR)
- UniSTS:16641

D6S416 (e-PCR), detects polymorphism
- UniSTS:52999

SGC38229 (e-PCR)
- UniSTS:65297

SHGC-84081 (e-PCR)
- UniSTS:104727

WI-11550 (e-PCR)
- UniSTS:45349

G20221 (e-PCR)
- UniSTS:40252

A005A32 (e-PCR)
- UniSTS:40253

RH92961 (e-PCR)
- UniSTS:89174

D6S416 (e-PCR), detects polymorphism
- UniSTS:84326

SHGC-82095 (e-PCR)
- UniSTS:103022

D6S416 (e-PCR), detects polymorphism
- UniSTS:23930

WI-12186 (e-PCR)
- UniSTS:66951

D6S1066 (e-PCR)
- UniSTS:39064

RH79598 (e-PCR)
- UniSTS:92846

RH18133 (e-PCR)
- UniSTS:76207

A006N46 (e-PCR)
- UniSTS:28608

RH45937 (e-PCR)
- UniSTS:44512

D6S1133E (e-PCR)
- UniSTS:35049

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables extracellular matrix structural constituent	ISS Inferred from Sequence or Structural Similarity more info
enables extracellular matrix structural constituent	RCA inferred from Reviewed Computational Analysis more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables signaling receptor binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in cell adhesion	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of cold-induced thermogenesis	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in regulation of cell adhesion	IEA Inferred from Electronic Annotation more info
involved_in regulation of cell migration	IEA Inferred from Electronic Annotation more info
involved_in regulation of embryonic development	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in basement membrane	IDA Inferred from Direct Assay more info	PubMed
located_in collagen-containing extracellular matrix	HDA more info	PubMed
colocalizes_with collagen-containing extracellular matrix	ISS Inferred from Sequence or Structural Similarity more info	PubMed
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info

General protein information

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Preferred Names: laminin subunit alpha-4

Names: laminin alpha 4 chain; laminin, alpha 4

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_008209.1 RefSeqGene

Range

5001..151695

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_433

mRNA and Protein(s)

NM_001105206.3 → NP_001098676.2 laminin subunit alpha-4 isoform 1 precursor

See identical proteins and their annotated locations for NP_001098676.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

AB210027, Z99289

Consensus CDS

CCDS43491.1

UniProtKB/Swiss-Prot

Q14731, Q14735, Q15335, Q16363, Q4LE44, Q5SZG8, Q9BTB8, Q9UE18, Q9UJN9

UniProtKB/TrEMBL

A0A0A0MQS9

Related

ENSP00000230538.7, ENST00000230538.12

Conserved Domains (5) summary

COG1196
Location:407 → 752

Smc; Chromosome segregation ATPase [Cell cycle control, cell division, chromosome partitioning]

cd00055
Location:187 → 238

EGF_Lam; Laminin-type epidermal growth factor-like domain; laminins are the major noncollagenous components of basement membranes that mediate cell adhesion, growth migration, and differentiation; the laminin-type epidermal growth factor-like module occurs in ...

cd00110
Location:1492 → 1624

LamG; Laminin G domain; Laminin G-like domains are usually Ca++ mediated receptors that can have binding sites for steroids, beta1 integrins, heparin, sulfatides, fibulin-1, and alpha-dystroglycans. Proteins that contain LamG domains serve a variety of ...

pfam06008
Location:298 → 554

Laminin_I; Laminin Domain I

pfam06009
Location:734 → 861

Laminin_II; Laminin Domain II
NM_001105207.3 → NP_001098677.2 laminin subunit alpha-4 isoform 2 precursor

See identical proteins and their annotated locations for NP_001098677.2

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses alternate splice sites in the 5' UTR and 5' coding region, compared to variant 1, resulting in a shorter protein (isoform 2), compared to isoform 1. Variants 2 and 3 encode the same isoform (2).

Source sequence(s)

AB210027, BC066552, Z99289

Consensus CDS

CCDS34514.1

UniProtKB/TrEMBL

A0A0A0MTC7, Q5D044

Related

ENSP00000429488.1, ENST00000522006.5

Conserved Domains (7) summary

COG1340
Location:419 → 717

COG1340; Uncharacterized coiled-coil protein, contains DUF342 domain [Function unknown]

cd00055
Location:187 → 238

EGF_Lam; Laminin-type epidermal growth factor-like domain; laminins are the major noncollagenous components of basement membranes that mediate cell adhesion, growth migration, and differentiation; the laminin-type epidermal growth factor-like module occurs in ...

cd00110
Location:1485 → 1617

LamG; Laminin G domain; Laminin G-like domains are usually Ca++ mediated receptors that can have binding sites for steroids, beta1 integrins, heparin, sulfatides, fibulin-1, and alpha-dystroglycans. Proteins that contain LamG domains serve a variety of ...

pfam06008
Location:289 → 547

Laminin_I; Laminin Domain I

pfam06009
Location:727 → 854

Laminin_II; Laminin Domain II

cl02488
Location:332 → 524

SPEC; Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; ...

cl09111
Location:503 → 602

Prefoldin; Prefoldin is a hexameric molecular chaperone complex, found in both eukaryotes and archaea, that binds and stabilizes newly synthesized polypeptides allowing them to fold correctly. The complex contains two alpha and four beta subunits, the two subunits ...
NM_001105208.3 → NP_001098678.1 laminin subunit alpha-4 isoform 3 precursor

See identical proteins and their annotated locations for NP_001098678.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) uses an alternate splice site in the 5' coding region, compared to variant 1, resulting in a protein (isoform 3) with a shorter, distinct C-terminus, compared to isoform 1. Variants 4 and 5 encode the same isoform (3).

Source sequence(s)

BC004241, BM014298, BP234809

Consensus CDS

CCDS43492.1

UniProtKB/Swiss-Prot

Q16363

Related

ENSP00000357627.4, ENST00000368638.5
NM_001105209.3 → NP_001098679.1 laminin subunit alpha-4 isoform 3 precursor

See identical proteins and their annotated locations for NP_001098679.1

Status: REVIEWED

Description

Transcript Variant: This variant (5) uses alternate splice sites in the 5' UTR and coding region, compared to variant 1, resulting in a protein (isoform 3) with a shorter, distinct C-terminus, compared to isoform 1. Variants 4 and 5 encode the same isoform (3).

Source sequence(s)

BC004241, BP234809

Consensus CDS

CCDS43492.1

UniProtKB/Swiss-Prot

Q16363

Related

ENSP00000398226.2, ENST00000453937.2
NM_002290.5 → NP_002281.3 laminin subunit alpha-4 isoform 2 precursor

See identical proteins and their annotated locations for NP_002281.3

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 5' coding region, compared to variant 1, resulting in a shorter protein (isoform 2), compared to isoform 1. Variants 2 and 3 encode the same isoform (2).

Source sequence(s)

AB210027, X91171, Z99289

Consensus CDS

CCDS34514.1

UniProtKB/TrEMBL

A0A0A0MTC7, Q5D044

Related

ENSP00000374114.4, ENST00000389463.9

Conserved Domains (7) summary

COG1340
Location:419 → 717

COG1340; Uncharacterized coiled-coil protein, contains DUF342 domain [Function unknown]

cd00055
Location:187 → 238

EGF_Lam; Laminin-type epidermal growth factor-like domain; laminins are the major noncollagenous components of basement membranes that mediate cell adhesion, growth migration, and differentiation; the laminin-type epidermal growth factor-like module occurs in ...

cd00110
Location:1485 → 1617

LamG; Laminin G domain; Laminin G-like domains are usually Ca++ mediated receptors that can have binding sites for steroids, beta1 integrins, heparin, sulfatides, fibulin-1, and alpha-dystroglycans. Proteins that contain LamG domains serve a variety of ...

pfam06008
Location:289 → 547

Laminin_I; Laminin Domain I

pfam06009
Location:727 → 854

Laminin_II; Laminin Domain II

cl02488
Location:332 → 524

SPEC; Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; ...

cl09111
Location:503 → 602

Prefoldin; Prefoldin is a hexameric molecular chaperone complex, found in both eukaryotes and archaea, that binds and stabilizes newly synthesized polypeptides allowing them to fold correctly. The complex contains two alpha and four beta subunits, the two subunits ...

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000006.12 Reference GRCh38.p14 Primary Assembly

Range

112107931..112254985 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047418770.1 → XP_047274726.1 laminin subunit alpha-4 isoform X2

UniProtKB/TrEMBL

A0A0A0MTC7, Q5D044
XM_047418769.1 → XP_047274725.1 laminin subunit alpha-4 isoform X1

UniProtKB/Swiss-Prot

Q14731, Q14735, Q15335, Q16363, Q4LE44, Q5SZG8, Q9BTB8, Q9UE18, Q9UJN9

UniProtKB/TrEMBL

A0A0A0MQS9

Conserved Domains (5) summary

COG1196
Location:407 → 752

Smc; Chromosome segregation ATPase [Cell cycle control, cell division, chromosome partitioning]

cd00055
Location:187 → 238

EGF_Lam; Laminin-type epidermal growth factor-like domain; laminins are the major noncollagenous components of basement membranes that mediate cell adhesion, growth migration, and differentiation; the laminin-type epidermal growth factor-like module occurs in ...

cd00110
Location:1492 → 1624

LamG; Laminin G domain; Laminin G-like domains are usually Ca++ mediated receptors that can have binding sites for steroids, beta1 integrins, heparin, sulfatides, fibulin-1, and alpha-dystroglycans. Proteins that contain LamG domains serve a variety of ...

pfam06008
Location:298 → 554

Laminin_I; Laminin Domain I

pfam06009
Location:734 → 861

Laminin_II; Laminin Domain II
XM_017010854.3 → XP_016866343.1 laminin subunit alpha-4 isoform X2

UniProtKB/TrEMBL

A0A0A0MTC7, Q5D044

Conserved Domains (7) summary

COG1340
Location:419 → 717

COG1340; Uncharacterized coiled-coil protein, contains DUF342 domain [Function unknown]

cd00055
Location:187 → 238

EGF_Lam; Laminin-type epidermal growth factor-like domain; laminins are the major noncollagenous components of basement membranes that mediate cell adhesion, growth migration, and differentiation; the laminin-type epidermal growth factor-like module occurs in ...

cd00110
Location:1485 → 1617

LamG; Laminin G domain; Laminin G-like domains are usually Ca++ mediated receptors that can have binding sites for steroids, beta1 integrins, heparin, sulfatides, fibulin-1, and alpha-dystroglycans. Proteins that contain LamG domains serve a variety of ...

pfam06008
Location:289 → 547

Laminin_I; Laminin Domain I

pfam06009
Location:727 → 854

Laminin_II; Laminin Domain II

cl02488
Location:332 → 524

SPEC; Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; ...

cl09111
Location:503 → 602

Prefoldin; Prefoldin is a hexameric molecular chaperone complex, found in both eukaryotes and archaea, that binds and stabilizes newly synthesized polypeptides allowing them to fold correctly. The complex contains two alpha and four beta subunits, the two subunits ...
XM_005266984.5 → XP_005267041.2 laminin subunit alpha-4 isoform X1

See identical proteins and their annotated locations for XP_005267041.2

UniProtKB/Swiss-Prot

Q14731, Q14735, Q15335, Q16363, Q4LE44, Q5SZG8, Q9BTB8, Q9UE18, Q9UJN9

UniProtKB/TrEMBL

A0A0A0MQS9

Conserved Domains (5) summary

COG1196
Location:407 → 752

Smc; Chromosome segregation ATPase [Cell cycle control, cell division, chromosome partitioning]

cd00055
Location:187 → 238

EGF_Lam; Laminin-type epidermal growth factor-like domain; laminins are the major noncollagenous components of basement membranes that mediate cell adhesion, growth migration, and differentiation; the laminin-type epidermal growth factor-like module occurs in ...

cd00110
Location:1492 → 1624

LamG; Laminin G domain; Laminin G-like domains are usually Ca++ mediated receptors that can have binding sites for steroids, beta1 integrins, heparin, sulfatides, fibulin-1, and alpha-dystroglycans. Proteins that contain LamG domains serve a variety of ...

pfam06008
Location:298 → 554

Laminin_I; Laminin Domain I

pfam06009
Location:734 → 861

Laminin_II; Laminin Domain II
XM_005266983.5 → XP_005267040.2 laminin subunit alpha-4 isoform X1

See identical proteins and their annotated locations for XP_005267040.2

UniProtKB/Swiss-Prot

Q14731, Q14735, Q15335, Q16363, Q4LE44, Q5SZG8, Q9BTB8, Q9UE18, Q9UJN9

UniProtKB/TrEMBL

A0A0A0MQS9

Conserved Domains (5) summary

COG1196
Location:407 → 752

Smc; Chromosome segregation ATPase [Cell cycle control, cell division, chromosome partitioning]

cd00055
Location:187 → 238

EGF_Lam; Laminin-type epidermal growth factor-like domain; laminins are the major noncollagenous components of basement membranes that mediate cell adhesion, growth migration, and differentiation; the laminin-type epidermal growth factor-like module occurs in ...

cd00110
Location:1492 → 1624

LamG; Laminin G domain; Laminin G-like domains are usually Ca++ mediated receptors that can have binding sites for steroids, beta1 integrins, heparin, sulfatides, fibulin-1, and alpha-dystroglycans. Proteins that contain LamG domains serve a variety of ...

pfam06008
Location:298 → 554

Laminin_I; Laminin Domain I

pfam06009
Location:734 → 861

Laminin_II; Laminin Domain II
XM_047418771.1 → XP_047274727.1 laminin subunit alpha-4 isoform X3

UniProtKB/TrEMBL

B7Z938