LAMB3

Summary

LAMB3 (laminin subunit beta 3, HGNC:6490) is a protein-coding gene on chromosome 1q32.2, encoding Laminin subunit beta-3 (Q13751). 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.

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.

Source: NCBI Gene 3914 — RefSeq curated summary.

At a glance

• Gene–disease (curated): junctional epidermolysis bullosa, non-Herlitz type (Definitive, GenCC) — +5 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 1,558 total — 144 pathogenic, 136 likely-pathogenic
• Phenotypes (HPO): 89
• Druggable target: yes
• MANE Select transcript: NM_000228

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6490
Approved symbol	LAMB3
Name	laminin subunit beta 3
Location	1q32.2
Locus type	gene with protein product
Status	Approved
Aliases	nicein-125kDa, kalinin-140kDa, BM600-125kDa
Ensembl gene	ENSG00000196878
Ensembl biotype	protein_coding
OMIM	150310
Entrez	3914

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 15 protein_coding

ENST00000356082, ENST00000367030, ENST00000391911, ENST00000415782, ENST00000455193, ENST00000887343, ENST00000887344, ENST00000887345, ENST00000887346, ENST00000887347, ENST00000887348, ENST00000887349, ENST00000887350, ENST00000962082, ENST00000962083

RefSeq mRNA: 3 — MANE Select: NM_000228 NM_000228, NM_001017402, NM_001127641

CCDS: CCDS1487

Canonical transcript exons

ENST00000356082 — 23 exons

Exon	Start	End
ENSE00000792096	209625648	209626026
ENSE00000792097	209626867	209626978
ENSE00000792099	209628035	209628190
ENSE00000792100	209629737	209629925
ENSE00000792101	209630615	209630735
ENSE00000792102	209632583	209632776
ENSE00000792103	209633070	209633133
ENSE00000792105	209637908	209637981
ENSE00000792106	209638534	209638648
ENSE00000841363	209649964	209650118
ENSE00001372269	209650917	209650981
ENSE00001377895	209627383	209627579
ENSE00001920394	209652369	209652425
ENSE00001950011	209614870	209615407
ENSE00002204869	209618452	209618659
ENSE00002208421	209617410	209617586
ENSE00002211996	209616471	209616624
ENSE00002236728	209622982	209623179
ENSE00002298569	209617907	209618048
ENSE00002310168	209622536	209622680
ENSE00002317073	209623505	209623725
ENSE00002386841	209623840	209624000
ENSE00003786002	209634447	209634638

Expression profiles

Bgee: expression breadth ubiquitous, 215 present calls, max score 96.70.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.8418 / max 1876.0743, expressed in 1095 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
17261	20.5513	273
17260	3.8339	939
17258	1.2379	370
17263	0.0865	43
17259	0.0550	15
17235	0.0299	14
17262	0.0247	14
17236	0.0226	12

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cartilage tissue	UBERON:0002418	96.70	gold quality
periodontal ligament	UBERON:0008266	94.87	gold quality
gingival epithelium	UBERON:0001949	94.19	gold quality
gingiva	UBERON:0001828	94.13	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.41	gold quality
jejunal mucosa	UBERON:0000399	93.11	gold quality
mucosa of transverse colon	UBERON:0004991	91.99	gold quality
skin of leg	UBERON:0001511	91.59	gold quality
ileal mucosa	UBERON:0000331	91.47	gold quality
skin of abdomen	UBERON:0001416	91.40	gold quality
esophagus mucosa	UBERON:0002469	91.37	gold quality
minor salivary gland	UBERON:0001830	90.33	gold quality
mouth mucosa	UBERON:0003729	90.29	gold quality
zone of skin	UBERON:0000014	90.15	gold quality
palpebral conjunctiva	UBERON:0001812	89.93	gold quality
lower esophagus mucosa	UBERON:0035834	89.45	gold quality
islet of Langerhans	UBERON:0000006	89.26	gold quality
duodenum	UBERON:0002114	88.91	gold quality
saliva-secreting gland	UBERON:0001044	88.19	gold quality
upper lobe of left lung	UBERON:0008952	88.02	gold quality
mammary duct	UBERON:0001765	87.84	gold quality
colonic mucosa	UBERON:0000317	87.70	gold quality
tongue squamous epithelium	UBERON:0006919	87.66	gold quality
epithelium of mammary gland	UBERON:0003244	87.59	gold quality
upper lobe of lung	UBERON:0008948	87.36	gold quality
mucosa of sigmoid colon	UBERON:0004993	86.77	gold quality
oral cavity	UBERON:0000167	86.35	gold quality
epithelium of nasopharynx	UBERON:0001951	86.31	silver quality
right lung	UBERON:0002167	85.70	gold quality
right adrenal gland	UBERON:0001233	85.16	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-MTAB-8530	yes	428.54
E-CURD-114	yes	345.07
E-MTAB-10662	yes	303.66
E-MTAB-8142	yes	91.64
E-HCAD-1	yes	19.90
E-GEOD-83139	yes	11.36
E-MTAB-6678	yes	9.00
E-GEOD-130148	yes	4.14
E-CURD-53	no	820.42
E-CURD-11	no	327.82
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GLI2, SMAD4

miRNA regulators (miRDB)

18 targeting LAMB3, 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-3119	99.92	71.34	2390
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6513-3P	99.59	69.77	1102
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-2113	99.58	71.22	1521
HSA-MIR-499A-3P	99.18	69.20	1392
HSA-MIR-499B-3P	99.18	69.27	1391
HSA-MIR-4254	99.11	65.15	1315
HSA-MIR-484	98.16	66.92	1074
HSA-MIR-4660	97.79	67.44	1328
HSA-MIR-10397-5P	97.31	69.06	710
HSA-MIR-4288	97.11	67.23	1636
HSA-MIR-1238-3P	95.27	62.25	552
HSA-MIR-6820-5P	94.04	61.13	161
HSA-MIR-4661-5P	93.34	67.13	400

Literature-anchored findings (GeneRIF, showing 40)

• Gene LAMB3 detected compound heterozygosity for the nonsense mutation R635X and a novel 2 bp deletion (1587delAG) resulting in a downstream premature termination codon. (PMID:11689492)
• Results identify the point during neoplastic progression in epithelia when the tumor suppressor p16 and laminin 5 are expressed and suggest that normal epithelia may use the same mechanism to generate non-dividing, motile cells for wound repair. (PMID:12875969)
• proteolytic processing of laminin-5 influences its interaction with alpha3beta1 integrin (PMID:14612440)
• co-cultures of epithelial cells and fibroblasts were studied to analyse the processing of laminin 5 alpha3, beta3, and gamma2 chains (PMID:15149852)
• Deletion analysis of laminin-beta3 indicated that the region comprising aa 726 to 875 of laminin-beta3 interacts with rotavirus enterotoxin NSP4. (PMID:15331737)
• In squamous cell carcinoma of the tongue and colorectal carcinoma, laminin 5 beta3 chain is important in the invasiveness of cancer cells. (PMID:15363037)
• homozygous frameshift mutation in LAMB3 was associated to illegitimate splicing leading to non-H junctional epidermolysis bullosa (PMID:15373767)
• the absolute mRNA levels generated from the laminin 5 genes do not determine the translated protein levels of the laminin 5 chains in keratinocytes; the expression of the laminin 5 genes may be controlled by common regulation mechanisms (PMID:15854126)
• DNA analysis revealed a compound heterozygote for mutations 2379delG and Q995X in the LAMB3 gene in Herlitz junctional epidermolysis bullosa (PMID:16147969)
• The uncoordinated production of chains of ln-5 in allergic asthma could have a bearing on the poor epithelial cell anchorage in these patients. (PMID:16179086)
• tumor cell migration on laminin-5 is inhibited by HYD1, a biologically active integrin-targeting peptide (PMID:16537560)
• Ln-5 is an important regulator of ADPKD cell proliferation and cystogenesis; Ln-5 gamma(2) chain and Ln-5-alpha(6)beta(4) integrin interaction both contribute to these phenotypic changes (PMID:16870608)
• Laminin-5 alone stimulates global changes in gene/protein expression in mesenchymal stem cells that lead to commitment of these cells to the osteogenic phenotype, and this correlates with extracellular matrix production. (PMID:17137774)
• Multiple second-site mutations, all correcting the germline mutation LAMB3 (628G–>A;Glu210Lys), are present in 2 unrelated non-Herlitz junctional epidermolysis bullosa patients with revertant mosaicism. (PMID:17476356)
• LM-332 is a crucial motility-promoting factor for B-CLL lymphocytes and is a potential constituent favoring the dissemination of B-CLL lymphocytes through vascular basement membranes and possibly lymph node compartments. (PMID:17482449)
• degradation [by Candida species] can exert functional disturbances on basement membrane integrity, possibly aiding Candida cell invasion into tissues (PMID:18284540)
• The expression of LAMB3 mrna was higher in malignant tissue and correlated with the depth of invasion and venous invasion in ESCC. (PMID:18331784)
• c.1945dupG mutation in Herlitz junctional epidermolysis bullosa (PMID:18387282)
• the alpha3 chain can assemble with only beta3-gamma2 heterodimer to form a heterotrimer via disulfide bonds (PMID:18603785)
• Ln-332 gamma2 may be a therapeutic target against metastatic colon cancer because a lowered beta3:gamma2 ratio would reduce expression of heterotrimeric Ln-332 and increase monomeric gamma2 secretion. (PMID:19383890)
• Histopathology of anti-laminin 5 mucous membrane pemphigoid is characterized by subepidermal blistering and a sparse to moderate superficial lymphohistiocytic infiltrate with neutrophils and/or eosinophils (PMID:19700013)
• Results suggest that laminin (LN)gamma2 and LNbeta3, in conjunction with MMP7, play a key role in the progression of biliary tract cancer. (PMID:19701966)
• Bisecting GlcNAc residues on laminin-332 down-regulate galectin-3-dependent keratinocyte motility. (PMID:19940114)
• The LAMB3 rs2566 variant CT/TT genotypes were associated with a significantly increased risk of cervical cancer, compared with the wild type CC genotype. (PMID:20163849)
• Cell surface COL17 can interact with laminin 332 and, together, participate in the adherence of a cell to the extracellular matrix. (PMID:21034821)
• These results suggest that epigenetic activation of LAMB3 and LAMC2 may play an important role in gastric carcinogenesis. (PMID:21345334)
• Data show laminin-332 (alpha3ss3gamma2)(Lm332) matrix supported adhesion of keratinocytes much more strongly and stably than purified Lm332. (PMID:22563463)
• invasive breast cancer cells confer an anoikis-resistant phenotype on myofibroblasts during tissue remodeling by inducing laminin-332 upregulation and integrin beta4 neoexpression (PMID:22673183)
• Laminin-5 is a useful biomarker in the evaluation of invasiveness in cervical adenocarcinoma. (PMID:22898004)
• we report a case of Herlitz junctional epidermolysis bullosa with a novel heterozygous mutation in LAMB3,c.1597G>A (p.Ala533Thr). (PMID:23278291)
• However, to our knowledge, this is the first report of dominant AI due to a LAMB3 mutation in the absence of JEB. (PMID:23632796)
• data further enhance the mutation spectrum of the LAMB3 and the COL7A1 genes, and also underscore the crucial roles of these genes in pathogenesis of epidermolysis bullosa (PMID:23769655)
• an 8-bp deletion (c.3446_3453del GACTGGAG) shifting the reading frame (p.Gly 1149Glufs*8) and a single nucleotide substitution (c.C3431A) generating an in-frame translation termination codon (p.Ser1144*)associated with amelogenesis imperfecta (PMID:23958762)
• Novel LAMB3 mutations cause non-syndromic amelogenesis imperfecta with variable expressivity. (PMID:24494736)
• Case Report: linear IgA/IgG bullous dermatosis with anti-laminin-332 autoantibodies. (PMID:24978847)
• LNbeta3 expression may play a key role in the progression and prognosis of pancreatic ductal adenocarcinoma. (PMID:25032755)
• Case Reports: Junctional epidermolysis bullosa with LAMB3 splice-site mutations. (PMID:25708563)
• Screening of ENAM and LAMB3 genes was performed by direct sequencing of genomic DNA from blood samples. (PMID:25769099)
• An algorithm combining CLDN10, HMGA2, and LAMB3 transcripts was able to discriminate tumors from BTL samples (94% sensitivity and 96% specificity in validation set). (PMID:25867809)
• The authors have identified a mutation in LAM3 causing lethal epidermolysis bullosa in a Balkan, Hungarian, population. Investigations into the genetic background of its unique carrier group, suggests that the estimated age of the mutation corresponds to the period of Roma migration in the Balkans. (PMID:27062385)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Lamb3	ENSMUSG00000026639
rattus_norvegicus	Lamb3	ENSRNOG00000006025

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), LAMB2 (ENSG00000172037), AGRN (ENSG00000188157), NTNG2 (ENSG00000196358), LAMA2 (ENSG00000196569), TMEFF1 (ENSG00000241697)

Protein

Protein identifiers

Laminin subunit beta-3 — Q13751 (reviewed: Q13751)

Alternative names: Epiligrin subunit beta, Kalinin B1 chain, Kalinin subunit beta, Laminin B1k chain, Laminin-5 subunit beta, Nicein subunit beta

All UniProt accessions (4): A0A0S2Z3R6, Q13751, Q5THA1, X1WI29

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-3 is a subunit of laminin-5 (laminin-332 or epiligrin/kalinin/nicein). Interacts with ECM1.

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

Tissue specificity. Found in the basement membranes (major component).

Disease relevance. Epidermolysis bullosa, junctional 1B, severe (JEB1B) [MIM:226700] A form of epidermolysis bullosa, a genodermatosis characterized by recurrent blistering, fragility of the skin and mucosal epithelia, and erosions caused by minor mechanical trauma. Junctional epidermolysis bullosa is characterized by blistering that occurs at the level of the lamina lucida in the skin basement membrane. JEB1B is an autosomal recessive, severe form characterized by bullous lesions appearing at birth, and extensive denudation of skin and mucous membranes that may be hemorrhagic. Death occurs usually within the first six months of life. Occasionally, children survive to teens. The disease is caused by variants affecting the gene represented in this entry. Epidermolysis bullosa, junctional 1A, intermediate (JEB1A) [MIM:226650] A form of epidermolysis bullosa, a genodermatosis characterized by recurrent blistering, fragility of the skin and mucosal epithelia, and erosions caused by minor mechanical trauma. Junctional epidermolysis bullosa is characterized by blistering that occurs at the level of the lamina lucida in the skin basement membrane. JEB1A is an autosomal recessive, non-lethal, adult form characterized by life-long blistering of the skin, associated with hair and tooth abnormalities. The disease is caused by variants affecting the gene represented in this entry. 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. 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. Domain VI is globular.

RefSeq proteins (3): NP_000219, NP_001017402, NP_001121113 (=MANE)

Domains & families (InterPro)

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

Pfam: PF00053, PF00055, PF23219, PF24973

UniProt features (66 total): disulfide bond 27, sequence variant 13, sequence conflict 8, domain 7, region of interest 3, coiled-coil region 3, glycosylation site 3, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13751-F1	78.55	0.23

Functional residue map

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

Disulfide bonds (27): 250–259, 252–279, 281–290, 293–313, 316–325, 318–343, 346–355, 358–376, 379–392, 381–399, 401–410, 413–428, 431–444, 433–451, 453–462, 465–478, 481–493, 483–500, 502–511, 519–531 …

Glycosylation sites (3): 220, 604, 810

Function

Pathways and Gene Ontology

Reactome pathways

18 pathways

ID	Pathway
R-HSA-1474228	Degradation of the extracellular matrix
R-HSA-2022090	Assembly of collagen fibrils and other multimeric structures
R-HSA-2214320	Anchoring fibril formation
R-HSA-3000157	Laminin interactions
R-HSA-3000171	Non-integrin membrane-ECM interactions
R-HSA-446107	Type I hemidesmosome assembly
R-HSA-8874081	MET activates PTK2 signaling
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-1474290	Collagen formation
R-HSA-1500931	Cell-Cell communication
R-HSA-162582	Signal Transduction
R-HSA-446728	Cell junction organization
R-HSA-6806834	Signaling by MET
R-HSA-8875878	MET promotes cell motility
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases

MSigDB gene sets: 463 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_FORMATION_OF_PRIMARY_GERM_LAYER, JAEGER_METASTASIS_DN, LI_PROSTATE_CANCER_EPIGENETIC, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, AREB6_01, NFKB_C, KIM_RESPONSE_TO_TSA_AND_DECITABINE_UP, FREAC3_01, KEGG_PATHWAYS_IN_CANCER, GOMF_EXTRACELLULAR_MATRIX_STRUCTURAL_CONSTITUENT, GOBP_BROWN_FAT_CELL_DIFFERENTIATION, GOBP_GASTRULATION, GOBP_ENDODERM_DEVELOPMENT, TGANTCA_AP1_C

GO Biological Process (5): cell adhesion (GO:0007155), epidermis development (GO:0008544), endodermal cell differentiation (GO:0035987), brown fat cell differentiation (GO:0050873), cell differentiation (GO:0030154)

GO Molecular Function (3): structural molecule activity (GO:0005198), extracellular matrix structural constituent (GO:0005201), protein binding (GO:0005515)

GO Cellular Component (4): extracellular region (GO:0005576), laminin-332 trimer (GO:0005610), extracellular matrix (GO:0031012), basement membrane (GO:0005604)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
Extracellular matrix organization	4
Collagen formation	1
Assembly of collagen fibrils and other multimeric structures	1
Cell junction organization	1
MET promotes cell motility	1
Biofilm formation	1
Non-integrin membrane-ECM interactions	1
Developmental Cell Lineages of the Exocrine Pancreas	1
Cell-Cell communication	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
extracellular matrix	2
cellular process	1
tissue development	1
endoderm formation	1
cell differentiation	1
fat cell differentiation	1
cellular developmental process	1
molecular_function	1
structural molecule activity	1
binding	1
cellular anatomical structure	1
laminin trimer	1
external encapsulating structure	1

Protein interactions and networks

STRING

1500 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LAMB3	LAMC2	Q13753	988
LAMB3	LAMA3	Q16787	985
LAMB3	LAMA4	Q16363	983
LAMB3	ITGB4	P16144	939
LAMB3	COL17A1	Q9UMD9	900
LAMB3	WDR72	Q3MJ13	708
LAMB3	LPGAT1	Q92604	697
LAMB3	COL7A1	Q02388	696
LAMB3	ITGA6	P23229	688
LAMB3	ENAM	Q9NRM1	674
LAMB3	SACK1H	Q6ZRV2	667
LAMB3	PPP2R5A	Q15172	664
LAMB3	A0A1W2PPA2	A0A1W2PPA2	642
LAMB3	COL4A1	P02462	635
LAMB3	AMTN	Q6UX39	621

IntAct

91 interactions, top by confidence:

A	B	Type	Score
C1QTNF9	C1QTNF9B	psi-mi:“MI:0914”(association)	0.780
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
FBXO6	MAN2B1	psi-mi:“MI:0914”(association)	0.640
CFTR	HAX1	psi-mi:“MI:0914”(association)	0.610
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
CLEC11A	VWA8	psi-mi:“MI:0914”(association)	0.530
NCEH1	CLGN	psi-mi:“MI:0914”(association)	0.530
PON2	NPC1	psi-mi:“MI:0914”(association)	0.530
C1orf54	EXTL3	psi-mi:“MI:0914”(association)	0.530
NOTCH2	ZNF316	psi-mi:“MI:0914”(association)	0.530
TIMP3	ZZEF1	psi-mi:“MI:0914”(association)	0.530
CFTR	CNOT1	psi-mi:“MI:0914”(association)	0.480
PDIA3	LAMB3	psi-mi:“MI:0408”(disulfide bond)	0.440
Ranbp2	POM121C	psi-mi:“MI:0914”(association)	0.350
MYEF2	PRMT5	psi-mi:“MI:0914”(association)	0.350
Tmed2		psi-mi:“MI:0914”(association)	0.350
LAMB3	MRPL58	psi-mi:“MI:0914”(association)	0.350
MKI67	ARHGAP10	psi-mi:“MI:0914”(association)	0.350
Creld2	P4HB	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
CFTR	POTEF	psi-mi:“MI:0914”(association)	0.350

BioGRID (106): ABCA2 (Affinity Capture-MS), HSPD1 (Affinity Capture-MS), ICT1 (Affinity Capture-MS), LAMB3 (Affinity Capture-MS), LGALS3BP (Affinity Capture-MS), STX3 (Affinity Capture-MS), TOP1 (Affinity Capture-MS), MED14 (Affinity Capture-MS), BAG2 (Affinity Capture-MS), SNRNP27 (Affinity Capture-MS), U2AF2 (Affinity Capture-MS), ATXN10 (Affinity Capture-MS), TIMMDC1 (Affinity Capture-MS), SFXN3 (Affinity Capture-MS), SLC25A25 (Affinity Capture-MS)

ESM2 similar proteins: A0JP86, A1A5Y0, A4D0S4, G5ECE3, O15230, P11046, P15215, P15800, P16144, P18563, P18564, P19137, P24043, P25391, P26010, P26011, P55268, P58459, P97607, Q13751, Q13753, Q16787, Q1EHB3, Q1RPR6, Q2KIT5, Q2QI47, Q5RB89, Q60438, Q60675, Q61001, Q61087, Q61092, Q61292, Q61789, Q68SA9, Q6AYF4, Q75N90, Q863C4, Q8BG22, Q8HZI9

Diamond homologs: A0JP86, A2ASQ1, G5ECE3, O00468, O00634, O09118, O15230, O75445, O75882, O95631, P02468, P11047, P15215, P19137, P24043, P25304, P25391, P31696, P34710, P97927, Q00174, Q01635, Q13751, Q13753, Q16363, Q16787, Q18823, Q19981, Q1LVF0, Q24567, Q24568, Q27262, Q2HXW4, Q2QI47, Q5RB89, Q5VV63, Q60675, Q61001, Q61087, Q61092

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
LAMB3	“form complex”	Laminin-5	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 108 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)	7	8.5×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

1558 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	144
Likely pathogenic	136
Uncertain significance	348
Likely benign	737
Benign	77

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1047957	NM_000228.3(LAMB3):c.323T>C (p.Leu108Pro)	Pathogenic
1047958	NM_000228.3(LAMB3):c.1634del (p.Gly545fs)	Pathogenic
1047959	NM_000228.3(LAMB3):c.2047del (p.Glu683fs)	Pathogenic
1069780	NM_000228.3(LAMB3):c.1427dup (p.Cys478fs)	Pathogenic
1070075	NM_000228.3(LAMB3):c.422dup (p.Thr142fs)	Pathogenic
1070854	NC_000001.10:g.(?209798983)(209812003_?)del	Pathogenic
1070928	NM_000228.3(LAMB3):c.2788C>T (p.Gln930Ter)	Pathogenic
1071051	NM_000228.3(LAMB3):c.823-1G>A	Pathogenic
1071957	NM_000228.3(LAMB3):c.2872del (p.Arg958fs)	Pathogenic
1072651	NM_000228.3(LAMB3):c.616C>T (p.Gln206Ter)	Pathogenic
1073710	NM_000228.3(LAMB3):c.221_225del (p.Pro74fs)	Pathogenic
1074201	NM_000228.3(LAMB3):c.565-1G>A	Pathogenic
1075457	NM_000228.3(LAMB3):c.1814_1827del (p.Ala605fs)	Pathogenic
1180738	NM_000228.3(LAMB3):c.1289-2_1296del	Pathogenic
1301693	NM_000228.3(LAMB3):c.3247C>T (p.Gln1083Ter)	Pathogenic
1364854	NM_000228.3(LAMB3):c.3239_3240del (p.Arg1080fs)	Pathogenic
1385498	NM_000228.3(LAMB3):c.3079A>T (p.Lys1027Ter)	Pathogenic
1397395	NM_000228.3(LAMB3):c.349C>T (p.Gln117Ter)	Pathogenic
1410657	NM_000228.3(LAMB3):c.282G>A (p.Trp94Ter)	Pathogenic
1416370	NM_000228.3(LAMB3):c.1897C>T (p.Gln633Ter)	Pathogenic
1421047	NM_000228.3(LAMB3):c.1657del (p.Cys553fs)	Pathogenic
1427996	NM_000228.3(LAMB3):c.2014del (p.Glu672fs)	Pathogenic
1430817	NM_000228.3(LAMB3):c.52C>T (p.Gln18Ter)	Pathogenic
1453284	NM_000228.3(LAMB3):c.2613_2614del (p.Glu871fs)	Pathogenic
1453477	NM_000228.3(LAMB3):c.484C>T (p.Gln162Ter)	Pathogenic
14539	NM_000228.3(LAMB3):c.1903C>T (p.Arg635Ter)	Pathogenic
1453922	NM_000228.3(LAMB3):c.2166C>G (p.Tyr722Ter)	Pathogenic
1453961	NM_000228.3(LAMB3):c.2422C>T (p.Gln808Ter)	Pathogenic
14541	NM_000228.3(LAMB3):c.124C>T (p.Arg42Ter)	Pathogenic
14542	NM_000228.3(LAMB3):c.904del (p.Trp302fs)	Pathogenic

SpliceAI

3177 predictions. Top by Δscore:

Variant	Effect	Δscore
1:209615403:CATGT:C	acceptor_gain	1.0000
1:209615405:TGT:T	acceptor_gain	1.0000
1:209615406:GTCT:G	acceptor_loss	1.0000
1:209615407:TC:T	acceptor_loss	1.0000
1:209615408:C:CC	acceptor_gain	1.0000
1:209615414:C:CT	acceptor_gain	1.0000
1:209615415:A:T	acceptor_gain	1.0000
1:209615417:A:AC	acceptor_gain	1.0000
1:209615417:A:C	acceptor_gain	1.0000
1:209615424:A:T	acceptor_gain	1.0000
1:209615427:A:T	acceptor_gain	1.0000
1:209616465:CCTCA:C	donor_loss	1.0000
1:209616466:CTCA:C	donor_loss	1.0000
1:209616467:TCACC:T	donor_loss	1.0000
1:209616468:CAC:C	donor_loss	1.0000
1:209616469:A:AC	donor_gain	1.0000
1:209616469:ACCTT:A	donor_loss	1.0000
1:209616470:C:CC	donor_gain	1.0000
1:209616470:C:CG	donor_loss	1.0000
1:209616470:CCTTT:C	donor_gain	1.0000
1:209616477:T:TA	donor_gain	1.0000
1:209616620:AATCC:A	acceptor_gain	1.0000
1:209616621:ATCC:A	acceptor_gain	1.0000
1:209616622:TCC:T	acceptor_gain	1.0000
1:209616623:CC:C	acceptor_gain	1.0000
1:209616623:CCC:C	acceptor_gain	1.0000
1:209616624:CC:C	acceptor_gain	1.0000
1:209616625:C:CC	acceptor_gain	1.0000
1:209616625:C:T	acceptor_gain	1.0000
1:209616626:T:A	acceptor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000056322 (1:209636380 G>T), RS1000088211 (1:209634817 C>T), RS1000169211 (1:209652442 G>A,T), RS1000262074 (1:209652631 C>T), RS1000285068 (1:209619217 C>T), RS1000308079 (1:209614784 T>C), RS1000389271 (1:209624956 GGAAGGAAAAAA>G), RS1000485079 (1:209620611 C>T), RS1000530933 (1:209615122 A>C,G,T), RS1000545293 (1:209645963 G>A), RS1000656335 (1:209651726 G>C), RS1000727574 (1:209640187 C>A,T), RS1000744365 (1:209646270 C>A,G), RS1000813901 (1:209642083 G>A), RS1000863171 (1:209634940 T>C)

Disease associations

OMIM: gene MIM:150310 | disease phenotypes: MIM:104530, MIM:226650, MIM:226700, MIM:209850, MIM:104500, MIM:131760

GenCC curated gene-disease

Disease	Classification	Inheritance
junctional epidermolysis bullosa, non-Herlitz type	Definitive	Autosomal recessive
junctional epidermolysis bullosa Herlitz type	Definitive	Autosomal recessive
junctional epidermolysis bullosa	Definitive	Autosomal recessive
amelogenesis imperfecta type 1A	Strong	Autosomal dominant
amelogenesis imperfecta type 1	Supportive	Autosomal dominant
generalized junctional epidermolysis bullosa non-Herlitz type	Supportive	Autosomal recessive

Mondo (10): amelogenesis imperfecta type 1A (MONDO:0007094), junctional epidermolysis bullosa, non-Herlitz type (MONDO:0009180), junctional epidermolysis bullosa Herlitz type (MONDO:0009182), junctional epidermolysis bullosa (MONDO:0017612), epidermolysis bullosa (MONDO:0006541), autism (MONDO:0005260), amelogenesis imperfecta (MONDO:0019507), epidermolysis bullosa simplex 1A, generalized severe (MONDO:0007550), amelogenesis imperfecta type 1 (MONDO:0015047), generalized junctional epidermolysis bullosa non-Herlitz type (MONDO:0019307)

Orphanet (8): Amelogenesis imperfecta (Orphanet:88661), Localized junctional epidermolysis bullosa (Orphanet:251393), Intermediate generalized junctional epidermolysis bullosa (Orphanet:79402), Severe generalized junctional epidermolysis bullosa (Orphanet:79404), Junctional epidermolysis bullosa inversa (Orphanet:79405), OBSOLETE: Junctional epidermolysis bullosa, non-Herlitz type (Orphanet:89840), Junctional epidermolysis bullosa (Orphanet:305), Autosomal dominant generalized epidermolysis bullosa simplex, severe form (Orphanet:79396)

HPO phenotypes

89 total (30 of 89 shown, HPO-id order):

HPO	Term
HP:0000003	Multicystic kidney dysplasia
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000014	Abnormality of the bladder
HP:0000016	Urinary retention
HP:0000070	Ureterocele
HP:0000072	Hydroureter
HP:0000081	Duplicated collecting system
HP:0000107	Renal cyst
HP:0000126	Hydronephrosis
HP:0000481	Abnormal cornea morphology
HP:0000668	Hypodontia
HP:0000670	Carious teeth
HP:0000679	Taurodontia
HP:0000705	Amelogenesis imperfecta
HP:0000939	Osteoporosis
HP:0000951	Abnormality of the skin
HP:0000969	Edema
HP:0000982	Palmoplantar keratoderma
HP:0000999	Pyoderma
HP:0001000	Abnormality of skin pigmentation
HP:0001030	Fragile skin
HP:0001056	Milia
HP:0001057	Aplasia cutis congenita
HP:0001075	Atrophic scars
HP:0001159	Syndactyly
HP:0001211	Abnormal fingertip morphology
HP:0001250	Seizure
HP:0001508	Failure to thrive

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST003200_1	Fentanyl consumption in laparoscopic-assisted colectomy (first 24 hours)	3.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007770	post-operative fentanyl consumption measurement

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D000567	Amelogenesis Imperfecta	C07.650.800.295.250; C07.793.700.295.250; C16.131.850.800.295.250
D001321	Autistic Disorder	F03.625.164.113.500
D004820	Epidermolysis Bullosa	C16.131.831.493; C16.320.850.275; C17.800.804.493; C17.800.827.275; C17.800.865.410
D016109	Epidermolysis Bullosa, Junctional	C16.131.831.493.170; C16.320.850.275.170; C17.800.804.493.170; C17.800.827.275.170; C17.800.865.410.170
C538240	Amelogenesis imperfecta local hypoplastic form (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)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2076222	LAMB3		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases abundance, increases expression	4
Cadmium	increases expression, increases abundance	3
Calcitriol	increases expression, affects cotreatment	3
Copper	affects binding, increases expression	3
Estradiol	affects cotreatment, decreases expression, increases expression	3
Tobacco Smoke Pollution	affects expression, increases expression	3
chloropicrin	decreases expression	2
(+)-JQ1 compound	decreases expression, increases expression	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, increases expression	2
Benzo(a)pyrene	decreases expression, decreases methylation	2
Mustard Gas	affects binding, increases degradation	2
Progesterone	decreases expression, increases expression, affects cotreatment	2
Valproic Acid	affects expression, increases expression	2
Cyclosporine	increases expression	2
Aflatoxin B1	increases expression, increases methylation	2
Cadmium Chloride	increases abundance, increases expression	2
Particulate Matter	increases expression, affects cotreatment, increases abundance	2
aristolochic acid I	increases expression	1
TAK-243	increases sumoylation	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment	1
bisphenol A	decreases expression	1
lead acetate	increases expression	1
methylselenic acid	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, increases expression, decreases expression	1
ethyl-p-hydroxybenzoate	increases expression	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	increases expression	1
pyrazolo(3,4-d)pyrimidine	affects expression	1
3,4-dichloroaniline	increases expression	1
beta-lapachone	increases expression	1
methylparaben	increases 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_D7TC	Ubigene A-549 LAMB3 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00336154	PHASE4	WITHDRAWN	Study to Evaluate the Efficacy of Tetracycline in Epidermolysis Bullosa
NCT01619670	PHASE4	TERMINATED	A Observational Study to Evaluate Apligraf(R) in Nonhealing Wounds of Subjects With Epidermolysis Bullosa
NCT07240649	PHASE4	NOT_YET_RECRUITING	Outcomes From Hyperbaric Oxygen (HBO2) Treatment for Emerging Indications
NCT07596927	PHASE4	ACTIVE_NOT_RECRUITING	Curcumin-Based Photodynamic Therapy in Epidermolysis Bullosa: Wound Healing, Quality of Life, and Salivary Biomarkers
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT00587223	PHASE3	TERMINATED	Safety and Efficacy of Apligraf in Nonhealing Wounds of Subjects With Junctional or Dystrophic Epidermolysis Bullosa (EB)
NCT06917690	PHASE3	RECRUITING	A Study to Learn About the Safety and Efficacy of the Drug Oleogel-S10 in Japanese Patients With Epidermolysis Bullosa
NCT01340235	PHASE3	UNKNOWN	Treatment of Dowling Maera Type of Epidermolysis Bullosa Simplex by Oral Erythromycin
NCT01749306	PHASE3	TERMINATED	A Study of the Efficacy and Safety of ABH001 in the Treatment of Patients With Epidermolysis Bullosa Who Have Wounds That Are Not Healing
NCT02384460	PHASE3	COMPLETED	ESSENCE Study: Efficacy and Safety of SD-101 Cream in Participants With Epidermolysis Bullosa
NCT02670330	PHASE3	TERMINATED	Open Label Extension Study to Evaluate the Long-term Safety of Zorblisa (SD-101-6.0) in Patients With Epidermolysis Bullosa
NCT03068780	PHASE3	COMPLETED	Phase III Efficacy and Safety Study of Oleogel-S10 in Epidermolysis Bullosa