LAMB2

Summary

LAMB2 (laminin subunit beta 2, HGNC:6487) is a protein-coding gene on chromosome 3p21.31, encoding Laminin subunit beta-2 (P55268). 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.

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, composed of 3 non identical chains: laminin alpha, beta and gamma (formerly A, B1, and B2, respectively), 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 beta chain isoform laminin, beta 2. The beta 2 chain contains the 7 structural domains typical of beta chains of laminin, including the short alpha region. However, unlike beta 1 chain, beta 2 has a more restricted tissue distribution. It is enriched in the basement membrane of muscles at the neuromuscular junctions, kidney glomerulus and vascular smooth muscle. Transgenic mice in which the beta 2 chain gene was inactivated by homologous recombination, showed defects in the maturation of neuromuscular junctions and impairment of glomerular filtration. Alternative splicing involving a non consensus 5’ splice site (gc) in the 5’ UTR of this gene has been reported. It was suggested that inefficient splicing of this first intron, which does not change the protein sequence, results in a greater abundance of the unspliced form of the transcript than the spliced form. The full-length nature of the spliced transcript is not known.

Source: NCBI Gene 3913 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Pierson syndrome (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 14
• Clinical variants (ClinVar): 1,360 total — 53 pathogenic, 44 likely-pathogenic
• Phenotypes (HPO): 110
• Druggable target: yes
• MANE Select transcript: NM_002292

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6487
Approved symbol	LAMB2
Name	laminin subunit beta 2
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Aliases	NPHS5
Ensembl gene	ENSG00000172037
Ensembl biotype	protein_coding
OMIM	150325
Entrez	3913

Gene structure

Transcript identifiers

Ensembl transcripts: 49 — 33 protein_coding, 14 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000305544, ENST00000418109, ENST00000462930, ENST00000464891, ENST00000467506, ENST00000469665, ENST00000477225, ENST00000477701, ENST00000480640, ENST00000483057, ENST00000483321, ENST00000484713, ENST00000486298, ENST00000488638, ENST00000493571, ENST00000494831, ENST00000498377, ENST00000538659, ENST00000542580, ENST00000884808, ENST00000884809, ENST00000884810, ENST00000884811, ENST00000884812, ENST00000884813, ENST00000884814, ENST00000884815, ENST00000884816, ENST00000921218, ENST00000960184, ENST00000960185, ENST00000960186, ENST00000960187, ENST00000960188, ENST00000960189, ENST00000960190, ENST00000960191, ENST00000960192, ENST00000960193, ENST00000960194, ENST00000960195, ENST00000960196, ENST00000960197, ENST00000960198, ENST00000960199, ENST00000960200, ENST00000960201, ENST00000960202, ENST00000960203

RefSeq mRNA: 1 — MANE Select: NM_002292 NM_002292

CCDS: CCDS2789

Canonical transcript exons

ENST00000305544 — 32 exons

Exon	Start	End
ENSE00001168039	49122163	49122370
ENSE00001168046	49122704	49123052
ENSE00001168051	49123132	49123373
ENSE00001600792	49132116	49132189
ENSE00001601025	49128661	49128819
ENSE00001643416	49124395	49124612
ENSE00001659981	49129839	49130018
ENSE00001709431	49125253	49125484
ENSE00001722060	49129245	49129324
ENSE00001728544	49131379	49131442
ENSE00001729160	49121114	49121362
ENSE00001734178	49130740	49130860
ENSE00001748125	49123728	49124100
ENSE00001776946	49130231	49130419
ENSE00001778336	49132491	49132663
ENSE00001788873	49131535	49131723
ENSE00001795065	49132270	49132405
ENSE00001797024	49129604	49129716
ENSE00001800160	49130950	49131152
ENSE00001845168	49132792	49133050
ENSE00003471805	49126365	49126497
ENSE00003491264	49129020	49129152
ENSE00003539865	49125967	49126159
ENSE00003555417	49123447	49123631
ENSE00003557396	49121944	49122085
ENSE00003579499	49121684	49121860
ENSE00003588134	49124190	49124286
ENSE00003606810	49124701	49124925
ENSE00003610996	49125747	49125890
ENSE00003628969	49125006	49125169
ENSE00003657931	49128458	49128585
ENSE00003674384	49121433	49121592

Expression profiles

Bgee: expression breadth ubiquitous, 268 present calls, max score 99.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 1.5624 / max 16.2727, expressed in 933 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
42222	77.0597	1644
42220	1.2217	774
42221	0.2694	125
42223	0.0714	14

Top tissues by expression

296 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	99.65	gold quality
right lobe of thyroid gland	UBERON:0001119	99.49	gold quality
stromal cell of endometrium	CL:0002255	99.47	gold quality
right ovary	UBERON:0002118	99.47	gold quality
left ovary	UBERON:0002119	99.47	gold quality
right adrenal gland cortex	UBERON:0035827	99.47	gold quality
left lobe of thyroid gland	UBERON:0001120	99.45	gold quality
right adrenal gland	UBERON:0001233	99.43	gold quality
ascending aorta	UBERON:0001496	99.43	gold quality
thoracic aorta	UBERON:0001515	99.43	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.43	gold quality
descending thoracic aorta	UBERON:0002345	99.41	gold quality
metanephros cortex	UBERON:0010533	99.41	gold quality
lower esophagus	UBERON:0013473	99.41	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.41	gold quality
endocervix	UBERON:0000458	99.40	gold quality
body of uterus	UBERON:0009853	99.40	gold quality
left adrenal gland cortex	UBERON:0035825	99.40	gold quality
right coronary artery	UBERON:0001625	99.39	gold quality
right atrium auricular region	UBERON:0006631	99.37	gold quality
left adrenal gland	UBERON:0001234	99.36	gold quality
left uterine tube	UBERON:0001303	99.33	gold quality
mucosa of stomach	UBERON:0001199	99.32	gold quality
nerve	UBERON:0001021	99.31	gold quality
tibial nerve	UBERON:0001323	99.31	gold quality
left coronary artery	UBERON:0001626	99.31	gold quality
aorta	UBERON:0000947	99.30	gold quality
popliteal artery	UBERON:0002250	99.27	gold quality
tibial artery	UBERON:0007610	99.27	gold quality
tendon of biceps brachii	UBERON:0008188	99.27	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-93593	yes	16.33
E-MTAB-6678	yes	12.74
E-GEOD-84465	yes	6.13
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HOXC10, HOXC13, MYC

miRNA regulators (miRDB)

9 targeting LAMB2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-29B-1-5P	98.86	68.35	1364
HSA-MIR-7155-5P	98.65	66.14	1290
HSA-MIR-1910-3P	98.44	67.51	1695
HSA-MIR-6511A-5P	98.13	67.47	1770

Literature-anchored findings (GeneRIF, showing 28)

• Laminin-10/11 and fibronectin differentially prevent apoptosis induced by serum removal via phosphatidylinositol 3-kinase/Akt- and MEK1/ERK-dependent pathways (Laminin 10; separate entry for Laminin 11). (PMID:11891225)
• Deficiency in LAMB2 causes congenital nephrosis with mesangial sclerosis and distinct eye abnormalities. (PMID:15367484)
• Hepalaminin, an autoantigen from chronic hepatitis C, consists of two domains of laminin beta-2 and a specific domain. (PMID:15603881)
• laminin isoform changes are associated with brain tumor invasion and angiogenesis [review] (PMID:16146715)
• Mutations in the LAMB2 gene encoding laminin beta2, a component of the glomerular basement membrane and the neuro-muscular junction are responsible for the characteristic renal and eye abnormalities of Pierson syndrome. (PMID:16898484)
• Recessive missense mutations in LAMB2 expand the clinical spectrum of LAMB2-associated disorders. (PMID:16912710)
• LAMB2 has to be considered as culprit of milder disorders including nephrosis and variable ocular anomalies. (PMID:16921188)
• Study summarizes recent progress concerning the molecular mechanisms of laminins in development and disease. (PMID:17426950)
• We demonstrated that overabundance of the beta2 chain of laminin is associated with increased basement membrane thickness and is possibly related to spermatogenic dysfunction (PMID:17804866)
• Milder phenotypes of Pearson Syndrome may be related to hypomorphic LAMB2 alleles. (PMID:17943323)
• Pierson syndrome is defined by the association of mental retardation, microcoria and DMS caused by mutation in LAMB2 gene (PMID:18065803)
• Study excluded LAMB2 as a candidate gene for Galloway-Mowat syndrome. (PMID:18594871)
• Loss-of-function mutations in laminin beta2 (LAMB2) cause a broad range of ocular pathology, emphasizing the importance of laminin beta2 in eye development. (PMID:18672223)
• LM alpha4 and beta2 have roles in in vitro migration and in vivo tumorigenicity of prostate cancer cells (PMID:19048114)
• beta2 chain-containing laminins (beta2-laminins) bound more avidly to alpha3beta1 and alpha7X2beta1 integrins than beta1 chain-containing laminins (beta1-laminins). (PMID:19147489)
• All previously reported and several novel LAMB2 mutations in relation to the associated phenotype in patients from 39 unrelated families, are reviewed. (PMID:20556798)
• Novel mutations in steroid-resistant nephrotic syndrome diagnosed in Tunisian children were detected in LAMB2. (PMID:21125408)
• Comprehensive gene sequencing revealed a novel LAMB2 variant (c.440A –> G; His147R) that was homozygous in the 9 living, affected family members, observed at a frequency of 2.1% in the Old Order Mennonite population, and absent in 91 non-Mennonite controls (PMID:21236492)
• No pathogenic LAMB2 mutations were found in the cohort of children with steroid-resistant focal segmental glomerulosclerosis. (PMID:24856380)
• Laminins 411 and 421 differentially promote tumor cell migration via alpha6beta1 integrin and MCAM (CD146). (PMID:24951930)
• 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) (PMID:27614294)
• In conclusion, we reported three Chinese cases with different LAMB2 mutations and different phenotypes, further broadening the range of eye and kidney pathology associated with mutations in LAMB2. (PMID:27925579)
• Collectively, these data show the pathogenicity of LAMB2-S80R and provide the first evidence of genetic modification of Alport phenotypes by variation in another GBM component. This (PMID:29263159)
• Age-related modulation of laminin beta1 versus beta2 chain expression changes the functional properties and phenotype of endothelial cells. The dysregulation of the extracellular matrix during vascular aging may contribute to age-associated impairment of organ function and fibrosis. (PMID:29599141)
• Development of neovascular glaucoma after intraocular surgery in Pierson syndrome. (PMID:33554690)
• Laminin beta2 variants associated with isolated nephropathy that impact matrix regulation. (PMID:33749661)
• Early-Onset Myopia and Retinal Detachment without Typical Microcoria or Severe Proteinuria due to a Novel LAMB2 Variant. (PMID:37678612)
• Expanding the spectrum of LAMB2: Pierson syndrome associated with neuromuscular junction disorder in two patients. (PMID:38723581)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	lamb2	ENSDARG00000002084
mus_musculus	Lamb2	ENSMUSG00000052911
rattus_norvegicus	Lamb2	ENSRNOG00000047768

Paralogs (27): USH2A (ENSG00000042781), LAMC3 (ENSG00000050555), LAMA3 (ENSG00000053747), LAMC2 (ENSG00000058085), NTN1 (ENSG00000065320), NTN4 (ENSG00000074527), ATRN (ENSG00000088812), LAMB4 (ENSG00000091128), LAMB1 (ENSG00000091136), LAMA1 (ENSG00000101680), MEGF8 (ENSG00000105429), MEGF9 (ENSG00000106780), ATRNL1 (ENSG00000107518), LAMA4 (ENSG00000112769), LAMA5 (ENSG00000130702), LAMC1 (ENSG00000135862), NTN5 (ENSG00000142233), HSPG2 (ENSG00000142798), TMEFF2 (ENSG00000144339), NTN3 (ENSG00000162068), NTNG1 (ENSG00000162631), EGFLAM (ENSG00000164318), AGRN (ENSG00000188157), NTNG2 (ENSG00000196358), LAMA2 (ENSG00000196569), LAMB3 (ENSG00000196878), TMEFF1 (ENSG00000241697)

Protein

Protein identifiers

Laminin subunit beta-2 — P55268 (reviewed: P55268)

Alternative names: Laminin B1s chain, Laminin-11 subunit beta, Laminin-14 subunit beta, Laminin-15 subunit beta, Laminin-3 subunit beta, Laminin-4 subunit beta, Laminin-7 subunit beta, Laminin-9 subunit beta, S-laminin subunit beta

All UniProt accessions (2): P55268, F5H520

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Laminin is a complex glycoprotein, consisting of three different polypeptide chains (alpha, beta, gamma), which are bound to each other by disulfide bonds into a cross-shaped molecule comprising one long and three short arms with globules at each end. Beta-2 is a subunit of laminin-3 (laminin-121 or S-laminin), laminin-4 (laminin-221 or S-merosin), laminin-7 (laminin-321 or KS-laminin), laminin-9 (laminin-421), laminin-11 (laminin-521), laminin-14 (laminin-423) and laminin-15 (laminin-523).

Subcellular location. Secreted. Extracellular space. Extracellular matrix. Basement membrane.

Disease relevance. Pierson syndrome (PIERS) [MIM:609049] An autosomal recessive disorder characterized by nephrotic syndrome with neonatal onset, diffuse mesangial sclerosis, and eye abnormalities with microcoria and hypoplasia of the ciliary and pupillary muscles. Death usually occurs within the first weeks of life. Patients who survive tend to show neurodevelopmental delay and visual loss. The disease is caused by variants affecting the gene represented in this entry. Nephrotic syndrome 5, with or without ocular abnormalities (NPHS5) [MIM:614199] A form of nephrotic syndrome, a renal disease clinically characterized by severe proteinuria, resulting in complications such as hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show non-specific histologic changes such as focal segmental glomerulosclerosis and diffuse mesangial proliferation. Some affected individuals have an inherited steroid-resistant form and progress to end-stage renal failure. NPHS5 is characterized by very early onset of progressive renal failure. A subset of patients may develop mild ocular anomalies, such as myopia, nystagmus, and strabismus. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The alpha-helical domains I and II are thought to interact with other laminin chains to form a coiled coil structure. Domains VI and IV are globular.

RefSeq proteins (1): NP_002283* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000742	EGF	Domain
IPR002049	LE_dom	Domain
IPR008211	Laminin_N	Domain
IPR013015	Laminin_IV_B	Domain
IPR050440	Laminin/Netrin_ECM	Family
IPR056558	LAMB1-4_helical	Domain
IPR056863	LMN_ATRN_NET-like_EGF	Domain

Pfam: PF00053, PF00055, PF21199, PF23219, PF24973

UniProt features (101 total): disulfide bond 54, domain 15, sequence variant 12, glycosylation site 7, region of interest 4, coiled-coil region 3, sequence conflict 2, signal peptide 1, chain 1, compositionally biased region 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P55268-F1	75.94	0.10

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 1532

Disulfide bonds (54): 283–292, 285–310, 312–321, 324–344, 347–356, 349–374, 377–386, 389–407, 410–423, 412–438, 440–449, 452–467, 470–484, 472–491, 493–502, 505–519, 522–534, 524–541, 543–552, 783–795 …

Glycosylation sites (7): 248, 368, 1085, 1249, 1308, 1348, 1499

Function

Pathways and Gene Ontology

Reactome pathways

16 pathways

ID	Pathway
R-HSA-3000157	Laminin interactions
R-HSA-3000171	Non-integrin membrane-ECM interactions
R-HSA-3000178	ECM proteoglycans
R-HSA-381426	Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-8874081	MET activates PTK2 signaling
R-HSA-8957275	Post-translational protein phosphorylation
R-HSA-9638630	Attachment of bacteria to epithelial cells
R-HSA-9913351	Formation of the dystrophin-glycoprotein complex (DGC)
R-HSA-9925563	Developmental Lineage of Pancreatic Ductal Cells
R-HSA-1474244	Extracellular matrix organization
R-HSA-162582	Signal Transduction
R-HSA-392499	Metabolism of proteins
R-HSA-597592	Post-translational protein modification
R-HSA-6806834	Signaling by MET
R-HSA-8875878	MET promotes cell motility
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases

MSigDB gene sets: 0 (showing top):

GO Biological Process (18): cell adhesion (GO:0007155), axon guidance (GO:0007411), neuromuscular junction development (GO:0007528), visual perception (GO:0007601), astrocyte development (GO:0014002), Schwann cell development (GO:0014044), positive regulation of cell adhesion (GO:0045785), axon extension involved in regeneration (GO:0048677), positive regulation of muscle cell differentiation (GO:0051149), radial glial cell differentiation (GO:0060019), retina development in camera-type eye (GO:0060041), metanephric podocyte development (GO:0072249), metanephric glomerular basement membrane development (GO:0072274), regulation of basement membrane organization (GO:0110011), positive regulation of integrin-mediated signaling pathway (GO:2001046), cell morphogenesis (GO:0000902), neuron projection development (GO:0031175), synapse organization (GO:0050808)

GO Molecular Function (5): integrin binding (GO:0005178), structural molecule activity (GO:0005198), extracellular matrix structural constituent (GO:0005201), structural constituent of synapse-associated extracellular matrix (GO:0150043), protein binding (GO:0005515)

GO Cellular Component (12): extracellular region (GO:0005576), basement membrane (GO:0005604), laminin-121 trimer (GO:0005608), endoplasmic reticulum lumen (GO:0005788), extracellular matrix (GO:0031012), neuromuscular junction (GO:0031594), synaptic cleft (GO:0043083), laminin-521 trimer (GO:0043260), extracellular exosome (GO:0070062), protein complex involved in cell-matrix adhesion (GO:0098637), laminin trimer (GO:0043256), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
Extracellular matrix organization	3
Metabolism of proteins	2
MET promotes cell motility	1
Post-translational protein modification	1
Biofilm formation	1
Non-integrin membrane-ECM interactions	1
Developmental Cell Lineages of the Exocrine Pancreas	1
Signaling by Receptor Tyrosine Kinases	1
Signaling by MET	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
glial cell development	2
extracellular matrix	2
cellular anatomical structure	2
laminin trimer	2
cellular process	1
axonogenesis	1
neuron projection guidance	1
synapse organization	1
sensory perception of light stimulus	1
astrocyte differentiation	1
Schwann cell differentiation	1
cell adhesion	1
regulation of cell adhesion	1
positive regulation of cellular process	1
regeneration	1
axon extension	1
sprouting of injured axon	1
muscle cell differentiation	1
positive regulation of cell differentiation	1
regulation of muscle cell differentiation	1
glial cell differentiation	1
camera-type eye development	1
anatomical structure development	1
podocyte development	1
metanephric podocyte differentiation	1
metanephric glomerular epithelial cell development	1
glomerular basement membrane development	1
metanephric glomerulus development	1
basement membrane organization	1
regulation of extracellular matrix organization	1
integrin-mediated signaling pathway	1
positive regulation of signal transduction	1
regulation of integrin-mediated signaling pathway	1
anatomical structure morphogenesis	1
neuron development	1
plasma membrane bounded cell projection organization	1
cell junction organization	1
signaling receptor binding	1
protein-containing complex binding	1
cell adhesion molecule binding	1

Protein interactions and networks

STRING

1262 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LAMB2	CD2AP	Q9Y5K6	690
LAMB2	LAMC2	Q13753	591
LAMB2	LAMC1	P11047	497
LAMB2	ACHE	P22303	492
LAMB2	COL6A1	P12109	451
LAMB2	LAMA2	P24043	427
LAMB2	COL6A2	P12110	420
LAMB2	NOA1	Q8NC60	408
LAMB2	NID2	Q14112	403
LAMB2	NID1	P14543	393
LAMB2	BDNF	P23560	389
LAMB2	ITGA5	P08648	380
LAMB2	KMO	O15229	371
LAMB2	LAMA4	Q16363	367
LAMB2	F5	P12259	366

IntAct

150 interactions, top by confidence:

A	B	Type	Score
ARRDC1	WWP2	psi-mi:“MI:0914”(association)	0.850
C1QTNF9	C1QTNF9B	psi-mi:“MI:0914”(association)	0.780
FBXO6	MAN2B1	psi-mi:“MI:0914”(association)	0.640
LAMB2	TSR2	psi-mi:“MI:0915”(physical association)	0.560
VWCE	ZNF316	psi-mi:“MI:0914”(association)	0.530
DEFA1	MANBA	psi-mi:“MI:0914”(association)	0.530
OS9	AGRN	psi-mi:“MI:0914”(association)	0.530
GPHA2	PLXNA2	psi-mi:“MI:0914”(association)	0.530
PLA2G10	CHEK1	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
PLAUR	XRCC3	psi-mi:“MI:0914”(association)	0.530
CLEC11A	VWA8	psi-mi:“MI:0914”(association)	0.530
CRP	QSOX1	psi-mi:“MI:0914”(association)	0.530
C1orf54	EXTL3	psi-mi:“MI:0914”(association)	0.530
ANTXR1	WFS1	psi-mi:“MI:0914”(association)	0.530
DNAJC3	DEDD	psi-mi:“MI:0914”(association)	0.530
EDN3	MGRN1	psi-mi:“MI:0914”(association)	0.530
NOTCH2	ZNF316	psi-mi:“MI:0914”(association)	0.530
VEGFB	LAMB2	psi-mi:“MI:0914”(association)	0.530
LAMB2		psi-mi:“MI:0915”(physical association)	0.370
LAMB2	caf1M	psi-mi:“MI:0915”(physical association)	0.370
NEC1	LAMB2	psi-mi:“MI:0915”(physical association)	0.370
LAMB2	HOXA1	psi-mi:“MI:0915”(physical association)	0.370
ATXN7	LAMB2	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (136): LAMB2 (Affinity Capture-MS), LAMB2 (Affinity Capture-MS), LAMB2 (Affinity Capture-MS), LAMB2 (Affinity Capture-MS), LAMB2 (Affinity Capture-MS), LAMB2 (Affinity Capture-MS), LAMB2 (Affinity Capture-MS), LAMB2 (Affinity Capture-MS), LAMB2 (Affinity Capture-MS), LAMB2 (Affinity Capture-MS), LAMB2 (Affinity Capture-MS), LAMB2 (Affinity Capture-MS), LAMB2 (Affinity Capture-MS), LAMB2 (Affinity Capture-MS), LAMB2 (Affinity Capture-MS)

ESM2 similar proteins: A0A6I8RMG7, A0JP86, A4D0S4, O54890, O70309, P02468, P02469, P05106, P0CY46, P11046, P11047, P13387, P13388, P15215, P15800, P18084, P18563, P18564, P19137, P24043, P25391, P35555, P55268, P80747, P98133, Q07441, Q18823, Q1LVF0, Q1RPR6, Q2KIT5, Q5RB89, Q60675, Q61220, Q61292, Q61526, Q61554, Q61555, Q62918, Q6AYF4, Q6UXH1

Diamond homologs: A2ASQ1, A4D0S4, O00468, O00634, O09118, O75445, O95631, P02469, P07942, P11046, P15800, P25304, P34710, P55268, P97927, Q01635, Q01636, Q05793, Q06561, Q13751, Q13753, Q16363, Q16787, Q19981, Q24567, Q24568, Q27262, Q2HXW4, Q2QI47, Q5RB89, Q61001, Q61087, Q61092, Q61292, Q61789, Q8BH27, Q8HZI9, Q8JHV6, Q8K3K1, Q8WTR8

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
LAMB2	“form complex”	Laminin-9	binding
HOXC13	“up-regulates quantity by expression”	LAMB2	“transcriptional regulation”
HOXC10	“up-regulates quantity by expression”	LAMB2	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 181 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
ERAD pathway	10	11.3×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

1360 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	53
Likely pathogenic	44
Uncertain significance	733
Likely benign	369
Benign	14

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1179149	NM_002292.4(LAMB2):c.1276del (p.His426fs)	Pathogenic
1323180	NM_002292.3(LAMB2):c.1037_1038del	Pathogenic
1323181	NM_002292.4(LAMB2):c.4285C>T (p.Arg1429Ter)	Pathogenic
1323182	NM_002292.4(LAMB2):c.3595C>T (p.Arg1199Ter)	Pathogenic
1333511	NM_002292.4(LAMB2):c.4904_4905del (p.Thr1635fs)	Pathogenic
1344739	NM_002292.4(LAMB2):c.4573C>T (p.Gln1525Ter)	Pathogenic
1366297	NM_002292.4(LAMB2):c.4201del (p.Ser1401fs)	Pathogenic
1377324	NM_002292.4(LAMB2):c.3882_3892del (p.Asn1294fs)	Pathogenic
1446226	NM_002292.4(LAMB2):c.3477_3483del (p.Gly1160fs)	Pathogenic
14529	NM_002292.4(LAMB2):c.3015del (p.Gln1006fs)	Pathogenic
14531	NM_002292.4(LAMB2):c.5258dup (p.Glu1754fs)	Pathogenic
14532	NM_002292.4(LAMB2):c.2067C>G (p.Tyr689Ter)	Pathogenic
14533	NM_002292.4(LAMB2):c.1122T>A (p.Cys374Ter)	Pathogenic
1453552	NM_002292.4(LAMB2):c.1390_1391insA (p.Arg464fs)	Pathogenic
14536	NM_002292.4(LAMB2):c.961T>C (p.Cys321Arg)	Pathogenic
14537	NM_002292.4(LAMB2):c.1478del (p.Cys493fs)	Pathogenic
14538	NM_002292.4(LAMB2):c.4804del (p.Gln1602fs)	Pathogenic
1455722	NM_002292.4(LAMB2):c.1934dup (p.Gly646fs)	Pathogenic
1456187	NM_002292.4(LAMB2):c.1241_1242dup (p.Met415fs)	Pathogenic
180395	NM_002292.4(LAMB2):c.2890C>T (p.Arg964Ter)	Pathogenic
1976270	NM_002292.4(LAMB2):c.3251G>A (p.Trp1084Ter)	Pathogenic
1998213	NM_002292.4(LAMB2):c.752_756dup (p.His253fs)	Pathogenic
2002665	NM_002292.4(LAMB2):c.2249dup (p.His750fs)	Pathogenic
2021063	NM_002292.4(LAMB2):c.3690_3697del (p.Ser1230fs)	Pathogenic
2115550	NM_002292.4(LAMB2):c.3328-1G>C	Pathogenic
2115551	NM_002292.4(LAMB2):c.2018+2T>C	Pathogenic
2116167	NM_002292.4(LAMB2):c.4806_4807del (p.Lys1603fs)	Pathogenic
2116168	NM_002292.4(LAMB2):c.2884+1del	Pathogenic
2203392	NM_002292.4(LAMB2):c.4198_4199del (p.Leu1400fs)	Pathogenic
2627166	NM_002292.4(LAMB2):c.1405+1G>A	Pathogenic

SpliceAI

4645 predictions. Top by Δscore:

Variant	Effect	Δscore
3:49121431:AC:A	donor_gain	1.0000
3:49121432:CC:C	donor_gain	1.0000
3:49121588:AGCAG:A	acceptor_gain	1.0000
3:49121589:GCAG:G	acceptor_gain	1.0000
3:49121590:CAG:C	acceptor_gain	1.0000
3:49121590:CAGC:C	acceptor_gain	1.0000
3:49121591:AG:A	acceptor_gain	1.0000
3:49121593:C:CC	acceptor_gain	1.0000
3:49121599:A:AC	acceptor_gain	1.0000
3:49121599:A:C	acceptor_gain	1.0000
3:49121717:G:GA	donor_gain	1.0000
3:49122178:T:TA	donor_gain	1.0000
3:49122188:G:C	donor_gain	1.0000
3:49122371:C:CC	acceptor_gain	1.0000
3:49122702:A:AC	donor_gain	1.0000
3:49122703:C:CC	donor_gain	1.0000
3:49123131:CCAG:C	donor_gain	1.0000
3:49123226:T:TA	donor_gain	1.0000
3:49123369:GGCAC:G	acceptor_gain	1.0000
3:49123371:CAC:C	acceptor_gain	1.0000
3:49123373:CCTAA:C	acceptor_loss	1.0000
3:49123374:C:CC	acceptor_gain	1.0000
3:49123375:T:G	acceptor_loss	1.0000
3:49123379:T:TC	acceptor_gain	1.0000
3:49123445:AC:A	donor_gain	1.0000
3:49123446:CC:C	donor_gain	1.0000
3:49123627:CACGC:C	acceptor_gain	1.0000
3:49123629:CGC:C	acceptor_gain	1.0000
3:49123630:GC:G	acceptor_gain	1.0000
3:49123631:CC:C	acceptor_gain	1.0000

AlphaMissense

11695 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:49131718:A:C	F155L	1.000
3:49131718:A:T	F155L	1.000
3:49131720:A:G	F155L	1.000
3:49131095:T:A	D257V	0.999
3:49131128:C:G	R246P	0.999
3:49131131:A:G	L245P	0.999
3:49131578:C:G	C202S	0.999
3:49131579:A:G	C202R	0.999
3:49131579:A:T	C202S	0.999
3:49131713:G:T	P157H	0.999
3:49131719:A:C	F155C	0.999
3:49132132:A:G	L148P	0.999
3:49132146:A:C	F143L	0.999
3:49132146:A:T	F143L	0.999
3:49132148:A:G	F143L	0.999
3:49132283:C:A	W124C	0.999
3:49132283:C:G	W124C	0.999
3:49132285:A:G	W124R	0.999
3:49132285:A:T	W124R	0.999
3:49132382:A:C	C91W	0.999
3:49132383:C:A	C91F	0.999
3:49132383:C:G	C91S	0.999
3:49132383:C:T	C91Y	0.999
3:49132384:A:G	C91R	0.999
3:49132384:A:T	C91S	0.999
3:49132392:C:G	C88S	0.999
3:49132393:A:T	C88S	0.999
3:49132509:G:C	C77W	0.999
3:49132510:C:G	C77S	0.999
3:49132510:C:T	C77Y	0.999

dbSNP variants (sampled 300 via entrez): RS1000541682 (3:49121030 G>A,C), RS1000553839 (3:49127547 T>G), RS1000688279 (3:49127242 T>A), RS1001083315 (3:49134568 G>A), RS1001232406 (3:49130569 C>T), RS1001792631 (3:49124427 G>C), RS1003011704 (3:49120622 C>G), RS1003044277 (3:49120782 C>T), RS1003251382 (3:49128033 A>C,G), RS1003574178 (3:49131807 C>G), RS1004020004 (3:49121732 T>G), RS1004458527 (3:49121854 C>A,T), RS1004583574 (3:49126800 T>C), RS1004695287 (3:49133270 A>C,T), RS1005857483 (3:49122651 CG>C)

Disease associations

OMIM: gene MIM:150325 | disease phenotypes: MIM:609049, MIM:249660, MIM:614199, MIM:601462

GenCC curated gene-disease

Disease	Classification	Inheritance
Pierson syndrome	Definitive	Autosomal recessive
LAMB2-related infantile-onset nephrotic syndrome	Strong	Autosomal recessive

Mondo (8): Pierson syndrome (MONDO:0012184), LAMB2-related infantile-onset nephrotic syndrome (MONDO:0013621), kidney disorder (MONDO:0005240), nephrotic syndrome (MONDO:0005377), focal segmental glomerulosclerosis (MONDO:0100313), atypical hemolytic-uremic syndrome (MONDO:0016244), congenital myasthenic syndrome (MONDO:0018940), glomerulonephritis (MONDO:0002462)

Orphanet (4): Pierson syndrome (Orphanet:2670), LAMB2-related infantile-onset nephrotic syndrome (Orphanet:306507), Atypical hemolytic uremic syndrome (Orphanet:2134), Congenital myasthenic syndrome (Orphanet:590)

HPO phenotypes

110 total (30 of 110 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000083	Renal insufficiency
HP:0000093	Proteinuria
HP:0000097	Focal segmental glomerulosclerosis
HP:0000099	Glomerulonephritis
HP:0000100	Nephrotic syndrome
HP:0000207	Triangular mouth
HP:0000218	High palate
HP:0000252	Microcephaly
HP:0000253	Progressive microcephaly
HP:0000303	Mandibular prognathia
HP:0000467	Neck muscle weakness
HP:0000486	Strabismus
HP:0000505	Visual impairment
HP:0000508	Ptosis
HP:0000510	Rod-cone dystrophy
HP:0000518	Cataract
HP:0000541	Retinal detachment
HP:0000545	Myopia
HP:0000558	Rieger anomaly
HP:0000568	Microphthalmia
HP:0000573	Retinal hemorrhage
HP:0000580	Pigmentary retinopathy
HP:0000597	Ophthalmoparesis
HP:0000609	Optic nerve hypoplasia
HP:0000618	Blindness
HP:0000639	Nystagmus
HP:0000790	Hematuria
HP:0000822	Hypertension
HP:0000969	Edema

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST003818_48	Resting heart rate	3.000000e-13
GCST004131_23	Inflammatory bowel disease	1.000000e-33
GCST004132_17	Crohn’s disease	3.000000e-23
GCST004133_11	Ulcerative colitis	8.000000e-20
GCST008357_20	Mood instability	4.000000e-11
GCST010320_99	PR interval	3.000000e-09
GCST010321_202	PR interval	4.000000e-10
GCST010698_80	Subcortical volume (min-P)	3.000000e-24
GCST010699_110	Brain morphology (min-P)	4.000000e-08
GCST010701_52	Cortical surface area (MOSTest)	1.000000e-16
GCST010702_36	Subcortical volume (MOSTest)	1.000000e-10
GCST010703_262	Brain morphology (MOSTest)	2.000000e-13
GCST011365_64	Myocardial infarction	8.000000e-10
GCST90020029_1173	Waist circumference adjusted for body mass index	1.000000e-10

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0008475	mood instability measurement
EFO:0004462	PR interval
EFO:0004346	neuroimaging measurement
EFO:0007789	BMI-adjusted waist circumference

MeSH disease descriptors (8)

Descriptor	Name	Tree numbers
D065766	Atypical Hemolytic Uremic Syndrome	C12.050.351.968.419.936.463.500; C12.200.777.419.936.463.500; C12.950.419.936.463.500; C15.378.050.141.610.500; C15.378.140.855.925.500.500; C15.378.243.937.925.500.500
D005921	Glomerulonephritis	C12.050.351.968.419.570.363; C12.200.777.419.570.363; C12.950.419.570.363
D005923	Glomerulosclerosis, Focal Segmental	C12.050.351.968.419.570.363.640; C12.200.777.419.570.363.660; C12.950.419.570.363.640
D007674	Kidney Diseases	C12.050.351.968.419; C12.200.777.419; C12.950.419
D020294	Myasthenic Syndromes, Congenital	C10.668.758.800; C16.320.590
D009404	Nephrotic Syndrome	C12.050.351.968.419.630.643; C12.200.777.419.630.643; C12.950.419.630.643
C565405	Mesangial Sclerosis, Diffuse Renal, with Ocular Abnormalities (supp.)
C537185	Pierson syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2364187 (PROTEIN COMPLEX GROUP)

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

52 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tetrachlorodibenzodioxin	affects expression, increases expression	3
bisphenol A	increases expression	2
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	2
Arsenic	increases abundance, increases ubiquitination, affects cotreatment, decreases expression	2
Nickel	decreases expression	2
Tobacco Smoke Pollution	affects expression	2
Valproic Acid	affects expression, decreases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	increases expression	1
methylmercuric chloride	decreases expression	1
kaempferol	increases expression	1
beta-lapachone	increases expression	1
arsenite	decreases expression, increases methylation	1
butyraldehyde	decreases expression	1
2-bromopalmitate	increases abundance, increases palmitoylation, decreases reaction	1
perfluorooctanoic acid	decreases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
3’,4’-dihydroxyflavone	increases expression	1
aflatoxin B2	increases methylation	1
chrysin	increases expression	1
di-n-butylphosphoric acid	affects expression	1
bisphenol S	increases expression	1
(+)-JQ1 compound	increases expression	1
Rosiglitazone	affects expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Azacitidine	increases expression	1
Benzo(a)pyrene	affects methylation	1
Cadmium	decreases reaction, increases abundance, increases palmitoylation	1
Chelating Agents	affects binding, decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D8P0	Ubigene HCT 116 LAMB2 KO	Cancer cell line	Male

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00067990	PHASE4	COMPLETED	Angiotensin II Blockade for Chronic Allograft Nephropathy
NCT00117078	PHASE4	COMPLETED	Aranesp® Monthly Preference Study - 2
NCT00117130	PHASE4	COMPLETED	Study to Evaluate Effectiveness of Aranesp®
NCT00132431	PHASE4	COMPLETED	START: Sensipar Treatment Algorithm to Reach K/DOQI Targets in Chronic Kidney Disease Subjects With Secondary Hyperparathyroidism
NCT00140985	PHASE4	COMPLETED	Antiproteinuric Efficacy of Losartan Potassium in Patients With Non-Diabetic Proteinuric Renal Diseases (0954-213)
NCT00246129	PHASE4	COMPLETED	CamTac Trial:Campath-Tacrolimus vs IL2R MoAb/Tacrolimus/MMF in Renal Transplantation
NCT00275535	PHASE4	COMPLETED	The Comparison of Tacrolimus and Sirolimus Immunosuppression Based Drug Regimens in Kidney Transplant Recipients
NCT00282217	PHASE4	COMPLETED	Study Evaluating Sirolimus in the Treatment of Kidney Transplant
NCT00289614	PHASE4	COMPLETED	Patients With Renal Impairment and Diabetes Undergoing Computed Tomography (CT)
NCT00290069	PHASE4	UNKNOWN	Renal Function Optimization With Mycophenolate Mofetil (MMF) Immunosuppressor Regimes (ALHAMBRA)
NCT00338468	PHASE4	TERMINATED	A Study to Assess Disability in Anemic Elderly Patients With Kidney Disease Receiving PROCRIT (Epoetin Alfa)
NCT00368901	PHASE4	COMPLETED	STAAR-2 Clinical Study
NCT00369733	PHASE4	COMPLETED	STAAR-3 Clinical Study
NCT00369772	PHASE4	COMPLETED	STAAR-1 Clinical Study
NCT00379899	PHASE4	COMPLETED	ADVANCE: Study to Evaluate Cinacalcet Plus Low Dose Vitamin D on Vascular Calcification in Subjects With Chronic Kidney Disease Receiving Hemodialysis
NCT00443508	PHASE4	UNKNOWN	Reduction or Discontinuation of CNI’s With Conversion to Everolimus-Based Immunosuppresion
NCT00452478	PHASE4	TERMINATED	Conversion From Standard Phosphate Binder Therapy to Fosrenol® (Lanthanum Carbonate) in Chronic Kidney Disease Stage 5
NCT00492518	PHASE4	COMPLETED	Acetylcysteine, Theophylline, and a Combination of Both in the Prophylaxis of Contrast-Induced Nephropathy
NCT00505102	PHASE4	UNKNOWN	Safe Renal Function In Long Term Heart Transplanted Patients
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00688480	PHASE4	COMPLETED	Do Xanthine Oxidase Inhibitors Reduce Both Left Ventricular Hypertrophy and Endothelial Dysfunction in Cardiovascular Patients With Renal Dysfunction?
NCT00863707	PHASE4	COMPLETED	A Study of the Safety and Tolerance of Regadenoson in Subjects With Renal Impairment
NCT01101698	PHASE4	UNKNOWN	Vitamin K2 and Vessel Calcification in Chronic Kidney Disease Patients
NCT01150201	PHASE4	COMPLETED	Aliskiren Combined With Losartan in Proteinuric, Non-diabetic Chronic Kidney Disease
NCT01155141	PHASE4	COMPLETED	Idiopathic Focal Segmental Glomerulosclerosis (FSGS) and Treatment With ACTH
NCT01228279	PHASE4	COMPLETED	Sympathetic Activity in Patients With End-stage Renal Disease on Peritoneal Dialysis
NCT01334333	PHASE4	COMPLETED	Comparison of Medication Adherence Between Once and Twice Daily Tacrolimus in Stable Renal Transplant Recipients
NCT01437943	PHASE4	TERMINATED	Effect of Short Term Aliskiren Treatment in Kidney Transplant Patients
NCT01545479	PHASE4	COMPLETED	Increased Renal Oxygenation and Angiotensin Converting Enzyme Inhibition
NCT01614431	PHASE4	COMPLETED	N Acetyl Cysteine for Cystinosis Patients
NCT01631149	PHASE4	COMPLETED	Effect of Deep BLock on Intraoperative Surgical Conditions
NCT01722513	PHASE4	UNKNOWN	Efficacy and Safety of Alprostadil Prevent Contrast Induced Nephropathy
NCT01985360	PHASE4	COMPLETED	ISCHEMIA-Chronic Kidney Disease Trial
NCT02311010	PHASE4	UNKNOWN	Practical Use of Advagraf de Novo After Kidney Transplantation According to Recipient Genetic Polymorphism
NCT02413073	PHASE4	COMPLETED	Whole Body Vibration in Kidney Disease
NCT02444013	PHASE4	UNKNOWN	Folic Acid for Prevention of Contrast Induced Nephropathy
NCT02663713	PHASE4	COMPLETED	A Randomized, Pharmacodynamic Comparison of Low Dose Ticagrelor to Clopidogrel in Patients With Prior Myocardial Infarction
NCT02707809	PHASE4	COMPLETED	Effects of Dexmedetomidine on Microcirculation of Kidney Transplant Recipient
NCT02761577	PHASE4	COMPLETED	A Prospective Study on Incidence and Prevention of Contrast-induced Nephropathy in Croatia
NCT03029351	PHASE4	TERMINATED	GLP-1 Receptor Agonist Therapy and Albuminuria in Patients With Type 2 Diabetes