LAMC1

Summary

LAMC1 (laminin subunit gamma 1, HGNC:6492) is a protein-coding gene on chromosome 1q25.3, encoding Laminin subunit gamma-1 (P11047). 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), have 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 gamma chain isoform laminin, gamma 1. The gamma 1 chain, formerly thought to be a beta chain, contains structural domains similar to beta chains, however, lacks the short alpha region separating domains I and II. The structural organization of this gene also suggested that it had diverged considerably from the beta chain genes. Embryos of transgenic mice in which both alleles of the gamma 1 chain gene were inactivated by homologous recombination, lacked basement membranes, indicating that laminin, gamma 1 chain is necessary for laminin heterotrimer assembly. It has been inferred by analogy with the strikingly similar 3’ UTR sequence in mouse laminin gamma 1 cDNA, that multiple polyadenylation sites are utilized in human to generate the 2 different sized mRNAs (5.5 and 7.5 kb) seen on Northern analysis.

Source: NCBI Gene 3915 — RefSeq curated summary.

At a glance

• GWAS associations: 15
• Clinical variants (ClinVar): 377 total
• Phenotypes (HPO): 1
• Druggable target: yes
• MANE Select transcript: NM_002293

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6492
Approved symbol	LAMC1
Name	laminin subunit gamma 1
Location	1q25.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000135862
Ensembl biotype	protein_coding
OMIM	150290
Entrez	3915

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000258341, ENST00000466964, ENST00000478064, ENST00000479499, ENST00000484114, ENST00000495918, ENST00000920737, ENST00000920738, ENST00000963244

RefSeq mRNA: 1 — MANE Select: NM_002293 NM_002293

CCDS: CCDS1351

Canonical transcript exons

ENST00000258341 — 28 exons

Exon	Start	End
ENSE00000922122	183140404	183140503
ENSE00000922123	183137669	183137827
ENSE00000922126	183134660	183134809
ENSE00000922127	183133406	183133550
ENSE00000922131	183128594	183128750
ENSE00000922134	183125397	183125550
ENSE00000922135	183124631	183124876
ENSE00000922136	183122063	183122251
ENSE00000922137	183121723	183121944
ENSE00000922138	183118034	183118146
ENSE00000922139	183117534	183117723
ENSE00000922140	183117320	183117442
ENSE00000922141	183116767	183116903
ENSE00000922145	183110488	183110654
ENSE00001160082	183142534	183145592
ENSE00001160088	183023420	183024134
ENSE00003459245	183135042	183135156
ENSE00003513441	183115520	183115637
ENSE00003522824	183136386	183136585
ENSE00003592883	183131299	183131378
ENSE00003595882	183126120	183126262
ENSE00003602607	183103328	183103632
ENSE00003607476	183130344	183130549
ENSE00003624892	183116577	183116675
ENSE00003642569	183114531	183114719
ENSE00003664036	183132400	183132537
ENSE00003672532	183108276	183108406
ENSE00003681197	183127226	183127404

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 99.28.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 77.0597 / max 777.5667, expressed in 1644 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
42222	77.0597	1644
7062	43.1850	1625
7065	6.9600	1215
7063	3.8573	1006
7066	0.7538	479
7074	0.4893	292
7064	0.4577	280

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	99.28	gold quality
visceral pleura	UBERON:0002401	98.97	gold quality
parietal pleura	UBERON:0002400	98.96	gold quality
pleura	UBERON:0000977	98.89	gold quality
calcaneal tendon	UBERON:0003701	98.74	gold quality
sural nerve	UBERON:0015488	98.68	gold quality
blood vessel layer	UBERON:0004797	98.66	gold quality
saphenous vein	UBERON:0007318	98.62	gold quality
placenta	UBERON:0001987	98.55	gold quality
mucosa of stomach	UBERON:0001199	98.52	gold quality
skin of hip	UBERON:0001554	98.52	gold quality
urethra	UBERON:0000057	98.50	gold quality
synovial joint	UBERON:0002217	98.43	gold quality
adipose tissue	UBERON:0001013	98.37	gold quality
subcutaneous adipose tissue	UBERON:0002190	98.37	gold quality
cauda epididymis	UBERON:0004360	98.35	gold quality
mammary duct	UBERON:0001765	98.29	gold quality
colonic epithelium	UBERON:0000397	98.26	gold quality
pericardium	UBERON:0002407	98.24	gold quality
connective tissue	UBERON:0002384	98.17	gold quality
tendon of biceps brachii	UBERON:0008188	98.16	gold quality
adipose tissue of abdominal region	UBERON:0007808	98.00	gold quality
omental fat pad	UBERON:0010414	97.97	gold quality
peritoneum	UBERON:0002358	97.96	gold quality
tendon	UBERON:0000043	97.93	gold quality
smooth muscle tissue	UBERON:0001135	97.91	gold quality
right lung	UBERON:0002167	97.86	gold quality
thoracic mammary gland	UBERON:0005200	97.84	gold quality
mammary gland	UBERON:0001911	97.76	gold quality
epithelium of mammary gland	UBERON:0003244	97.67	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-9543	yes	14.72
E-CURD-112	yes	8.14
E-GEOD-84465	yes	7.91
E-GEOD-83139	yes	6.64
E-GEOD-110499	no	733.34
E-MTAB-6678	no	3.88
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPB, GLI3, KLF4, NFKB, NR2F1, SMAD3, SP1, TFE3

miRNA regulators (miRDB)

232 targeting LAMC1, 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-3163	100.00	77.23	8605
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-12121	99.99	66.64	255
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-433-3P	99.98	69.37	1203

Literature-anchored findings (GeneRIF, showing 40)

• 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)
• Enhanced and specialized expression patterns of alpha 1 and gamma 1 laminins distinctly associate these two laminins with the Alzheimer disease. (PMID:12111806)
• The neurite outgrowth domain of gamma 1 laminin accumulates heavily in the floor plate region, in the notochord and in GFAP-immunoreactive glial fibers of the embryonic spinal cord. (PMID:12526023)
• mRNA encoding laminin-alpha1, -beta1, and -gamma1 chains was expressed in 90% of endometriotic lesions. (PMID:12615822)
• Data suggest that laminin-10 (alpha5beta1gamma1) is required for hair follicle development and report the first use of exogenous protein to correct a cutaneous developmental defect. (PMID:12743034)
• Basement membrane formation is inhibited by a nidogen-laminin gamma1-chain fragment in skin-organotypic cultures. (PMID:15159456)
• Expression of LAMC1 in glioblastoma is inhibited by indomethacin. Indomethacin inhibits cyclooxygenases and is an NSAID drug. (PMID:15561105)
• prostate cancer cells expressing high levels of MT1-MMP have increased invasive potential through their ability to degrade and invade Ln-10 barriers (PMID:15967115)
• laminin isoform changes are associated with brain tumor invasion and angiogenesis [review] (PMID:16146715)
• a polymorphism in the promoter of LAMC1 may increase the susceptibility to early-onset pelvic organ prolapse (PMID:17021862)
• gamma1 laminin is selectively overexpressed in reactive astrocytes of the amyotrophic lateral sclerosis spinal cord (PMID:17554784)
• In embryonic stem cells deficient in laminins, due to lamc1 (laminin gamma1) deletion, vascular development and organization were largely unaffected. (PMID:18073332)
• Laminin isoforms containing the gamma3 chain are unable to bind to integrins due to the absence of the glutamic acid residue conserved in the C-terminal regions of the gamma1 and gamma2 chains (PMID:18697739)
• laminin-111 (alpha(1), beta(1), gamma(1)), which is expressed during embryonic development but absent in normal or dystrophic skeletal muscle, increased alpha(7)-integrin expression in mouse and DMD patient myoblasts (PMID:19416897)
• Several LAMC1 single nucleotide polymorphisms exist with significant differences between African American and Caucasian women, but no association found between any LAMC1 variant and advanced pelvic organ prolapse. (PMID:20223449)
• The nano-structure of the laminin gamma-1 short arm was determined. In solution, it adapts an extended conformation. (PMID:20688161)
• Laminin-5 gamma2 chain and SPARC may play roles in the progression of esophageal squamous cell carcinoma and their simultaneous expression is correlated with poorer prognosis. (PMID:21192846)
• results suggest that Lm3B11/3B21 may be required for normal mature vessels and interfere with tumor angiogenesis (PMID:21276136)
• LAMC1 is significantly associated with premature ovarian failure, and specifically, possession of at least one HT1 was associated with susceptibility to premature ovarian failure. (PMID:22321639)
• Single-nucleotide polymorphisms (SNPs) representing 99% coverage of LAMC1 were genotyped. There was no association between SNP rs10911193 and advanced pelvic organ prolapse. There was a trend toward significance for SNPs rs1413390, rs20563, and rs20558. (PMID:22342894)
• Mutations in the coding sequence of LAMC1 and DLGH1 may not be associated with Mayer-Rokitansky-Kuster-Hauser Syndrome. (PMID:22377151)
• Overexpression of laminin gamma1 immunoreactivity and alteration of its staining pattern may serve as a useful biomarker in serous tubal intraepithelial carcinoma. (PMID:22892598)
• Autoantibodies in anti-p200 pemphigoid sera are pathogenic while pathogenicity is not mediated by autoantibodies against laminin gamma1. (PMID:22911854)
• Letter: a small but distinct subgroup of both systemic and cutaneous lupus erythematosus patients has antibodies against the C-terminus of laminin gamma1. (PMID:22968451)
• LAMC1 polymorphism could be a protective factor for SLE. (PMID:23039241)
• Results suggest that laminin gamma1 expression is associated with meningioma grades and could play a role in enhancing tumor invasion. (PMID:23053286)
• Genetic polymorphism of LAMC1 gene is associated in the pathogenesis of colorectal cancers. (PMID:23266556)
• results demonstrate that mutation in either NID1 or LAMC1 disrupts the interaction NID1-LAMC1 complex; findings implicate the extracellular matrix in the pathogenesis of Dandy-Walker spectrum disorders (PMID:23674478)
• carbohydrate moiety (alpha-Gal) on laminin gamma-1 and collagen alpha-1 (VI) chain are possibly common IgE-reactive proteins in the Japanese patients with beef allergy (PMID:24180678)
• These findings document a pathogenic potential of antibodies targeting the laminin gamma1 N-terminus. (PMID:24300951)
• Case Report: occurrence of anti-laminin-gamma1 pemphigoid in a case of autosomal recessive congenital ichthyosis. (PMID:24733442)
• Data showed that LAMC1 expression is directly regulated by miR-29s. (PMID:24820027)
• Laminins 411 and 421 differentially promote tumor cell migration via alpha6beta1 integrin and MCAM (CD146). (PMID:24951930)
• The identification of laminin gamma 1 (LAMC1) and myeloid cell leukemia 1 (MCL1) as direct targets of miR-22 and miR-29a, respectively, suggested a tumor-suppressive role of these miRNAs. (PMID:26052614)
• Case Report: Anti-laminin-gamma 1 pemphigoid in patient with generalized pustular psoriasis and psoriasis vulgaris. (PMID:26074471)
• LAMC1 may contribute to the development and progression of uterine carcinoma, likely through enhancing tumor cell motility and invasion. (PMID:26343160)
• Our results show that miR-181a is down-regulated in glioblastoma multiforme (GBM) patients. The three target genes, ANGPT2, ARHGAP18 and LAMC1, are negatively correlated with the expression of miR-181a. Moreover, high expression of ANGPT2 or LAMC1 together with large size of GBM is correlated with a shorter median overall survival (PMID:27176932)
• The rs780094 [1.34 (1.21-1.49); p = 8.57 x 10(-8) ] on chr 2 at the glucokinase regulatory protein (GCKR) locus was similarly significantly associated, while the rs10911205 [1.29 (1.16-1.44); p = 3.52 x 10(-6) ] on chr1 at the laminin subunit gamma-1 (LAMC1) locus showed suggestive association with disease. (PMID:27599772)
• miR-506 acts as a tumor suppressor and inhibits malignancy of colorectal cancer cells through directly targeting LAMC1. (PMID:27993882)
• Further gene expression analyses demonstrated significantly higher expression of LAMC1 gene in colorectal cancer (CRC) tumor tissues than that in adjacent non-cancerous tissues (P = 0.0004). These findings strongly suggest that the functional SNP located at TFBSs, rs6695837 might contribute to CRC susceptibility, and the exact biological mechanism awaits further research. (PMID:28039327)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	lamc2	ENSDARG00000068288
mus_musculus	Lamc1	ENSMUSG00000026478
rattus_norvegicus	Lamc1	ENSRNOG00000002680

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), NTN5 (ENSG00000142233), HSPG2 (ENSG00000142798), TMEFF2 (ENSG00000144339), NTN3 (ENSG00000162068), NTNG1 (ENSG00000162631), EGFLAM (ENSG00000164318), LAMB2 (ENSG00000172037), AGRN (ENSG00000188157), NTNG2 (ENSG00000196358), LAMA2 (ENSG00000196569), LAMB3 (ENSG00000196878), TMEFF1 (ENSG00000241697)

Protein

Protein identifiers

Laminin subunit gamma-1 — P11047 (reviewed: P11047)

Alternative names: Laminin B2 chain, Laminin-1 subunit gamma, Laminin-10 subunit gamma, Laminin-11 subunit gamma, Laminin-2 subunit gamma, Laminin-3 subunit gamma, Laminin-4 subunit gamma, Laminin-6 subunit gamma, Laminin-7 subunit gamma, Laminin-8 subunit gamma, Laminin-9 subunit gamma, S-laminin subunit gamma

All UniProt accessions (2): P11047, R4GNC7

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. As a subunit of laminin-1 (also known as laminin-111 or EHS laminin), it is involved in the stimulation of agrin-induced receptor clustering through a MuSK-independent pathway.

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. Gamma-1 is a subunit of laminin-1 (laminin-111 or EHS laminin), laminin-2 (laminin-211 or merosin), laminin-3 (laminin-121 or S-laminin), laminin-4 (laminin-221 or S-merosin), laminin-6 (laminin-311 or K-laminin), laminin-7 (laminin-321 or KS-laminin), laminin-8 (laminin-411), laminin-9 (laminin-421), laminin-10 (laminin-511) and laminin-11 (laminin-521). Interacts with SVEP1.

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

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

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_002284* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000034	Laminin_IV	Domain
IPR000742	EGF	Domain
IPR002049	LE_dom	Domain
IPR008211	Laminin_N	Domain
IPR050440	Laminin/Netrin_ECM	Family
IPR056863	LMN_ATRN_NET-like_EGF	Domain

Pfam: PF00052, PF00053, PF00055, PF24973

UniProt features (86 total): disulfide bond 43, domain 14, glycosylation site 14, sequence variant 6, modified residue 2, helix 2, signal peptide 1, chain 1, region of interest 1, coiled-coil region 1, sequence conflict 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
5XAU	X-RAY DIFFRACTION	1.8
8DMK	ELECTRON MICROSCOPY	3.7
7CEC	ELECTRON MICROSCOPY	3.9
9AZ3	ELECTRON MICROSCOPY	3.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P11047-F1	76.73	0.17

Antibody-complex structures (SAbDab): 1 — 7CEC

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 (2): 1149, 1493

Disulfide bonds (43): 286–295, 288–305, 307–316, 319–339, 342–351, 344–367, 370–379, 382–395, 398–410, 400–416, 418–427, 430–442, 445–456, 447–463, 465–474, 477–492, 724–733, 726–740, 742–751, 754–770 …

Glycosylation sites (14): 60, 134, 576, 650, 1022, 1107, 1161, 1175, 1205, 1223, 1241, 1380, 1395, 1439

Function

Pathways and Gene Ontology

Reactome pathways

22 pathways

ID	Pathway
R-HSA-1474228	Degradation of the extracellular matrix
R-HSA-3000157	Laminin interactions
R-HSA-3000171	Non-integrin membrane-ECM interactions
R-HSA-3000178	ECM proteoglycans
R-HSA-373760	L1CAM interactions
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-9619665	EGR2 and SOX10-mediated initiation of Schwann cell myelination
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-1266738	Developmental Biology
R-HSA-1474244	Extracellular matrix organization
R-HSA-162582	Signal Transduction
R-HSA-392499	Metabolism of proteins
R-HSA-422475	Axon guidance
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
R-HSA-9675108	Nervous system development

MSigDB gene sets: 469 (showing top): GOBP_NEUROMUSCULAR_JUNCTION_DEVELOPMENT, TGGTGCT_MIR29A_MIR29B_MIR29C, VERHAAK_AML_WITH_NPM1_MUTATED_DN, AP1_01, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, SWEET_KRAS_ONCOGENIC_SIGNATURE, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_POSITIVE_REGULATION_OF_MUSCLE_CELL_DIFFERENTIATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GNF2_PTX3, CTATGCA_MIR153, GOBP_REGULATION_OF_EXTRACELLULAR_MATRIX_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_CELL_ADHESION, GTGCCTT_MIR506

GO Biological Process (18): cell adhesion (GO:0007155), signal transduction (GO:0007165), endoderm development (GO:0007492), cell migration (GO:0016477), extracellular matrix disassembly (GO:0022617), regulation of cell adhesion (GO:0030155), regulation of cell migration (GO:0030334), hemidesmosome assembly (GO:0031581), substrate adhesion-dependent cell spreading (GO:0034446), maintenance of blood-brain barrier (GO:0035633), positive regulation of cell adhesion (GO:0045785), regulation of embryonic development (GO:0045995), positive regulation of epithelial cell proliferation (GO:0050679), positive regulation of muscle cell differentiation (GO:0051149), protein-containing complex assembly (GO:0065003), regulation of basement membrane organization (GO:0110011), positive regulation of integrin-mediated signaling pathway (GO:2001046), tissue development (GO:0009888)

GO Molecular Function (2): extracellular matrix structural constituent (GO:0005201), extracellular matrix constituent conferring elasticity (GO:0030023)

GO Cellular Component (10): extracellular region (GO:0005576), basement membrane (GO:0005604), laminin-111 trimer (GO:0005606), obsolete extracellular space (GO:0005615), endoplasmic reticulum lumen (GO:0005788), extracellular matrix (GO:0031012), laminin-511 trimer (GO:0043259), laminin-521 trimer (GO:0043260), extracellular exosome (GO:0070062), protein complex involved in cell-matrix adhesion (GO:0098637)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
Extracellular matrix organization	4
Metabolism of proteins	2
Nervous system development	2
Axon guidance	1
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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
laminin trimer	3
cellular process	2
regulation of cellular process	2
cell adhesion	2
extracellular matrix	2
cell communication	1
signaling	1
cellular response to stimulus	1
tissue development	1
cell motility	1
cellular component disassembly	1
extracellular matrix organization	1
cell migration	1
regulation of cell motility	1
cell-substrate junction assembly	1
cell-substrate adhesion	1
tissue homeostasis	1
regulation of cell adhesion	1
positive regulation of cellular process	1
embryo development	1
regulation of multicellular organismal development	1
positive regulation of cell population proliferation	1
epithelial cell proliferation	1
regulation of epithelial cell proliferation	1
muscle cell differentiation	1
positive regulation of cell differentiation	1
regulation of muscle cell differentiation	1
cellular component assembly	1
protein-containing complex organization	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 development	1
structural molecule activity	1
extracellular matrix structural constituent	1
structural molecule activity conferring elasticity	1
cellular anatomical structure	1
endoplasmic reticulum	1

Protein interactions and networks

STRING

2260 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LAMC1	LAMB1	P07942	973
LAMC1	NID2	Q14112	919
LAMC1	NID1	P14543	894
LAMC1	COL4A1	P02462	826
LAMC1	LAMA5	O15230	822
LAMC1	LAMA4	Q16363	818
LAMC1	FAT1	Q14517	774
LAMC1	LAMA2	P24043	771
LAMC1	COL27A1	Q8IZC6	766
LAMC1	RMC1	Q96DM3	749
LAMC1	COL4A2	P08572	747
LAMC1	COL1A1	P02452	727
LAMC1	COL24A1	Q17RW2	716
LAMC1	LAMA1	P25391	696
LAMC1	COL5A1	P20908	682

IntAct

113 interactions, top by confidence:

A	B	Type	Score
ARRDC1	WWP2	psi-mi:“MI:0914”(association)	0.850
TSG101	VPS37C	psi-mi:“MI:0914”(association)	0.780
C1QTNF9	C1QTNF9B	psi-mi:“MI:0914”(association)	0.780
PSMC5	PSMD11	psi-mi:“MI:0914”(association)	0.730
FAM9C	NDC80	psi-mi:“MI:0914”(association)	0.670
CAMKV	AP3B1	psi-mi:“MI:0914”(association)	0.640
FBXO6	MAN2B1	psi-mi:“MI:0914”(association)	0.640
TGFB1	NMT2	psi-mi:“MI:0914”(association)	0.530
PNLIP	LAMC1	psi-mi:“MI:0914”(association)	0.530
ABRAXAS1	LAMC1	psi-mi:“MI:0914”(association)	0.530
TXLNB	LAMC1	psi-mi:“MI:0914”(association)	0.530
YWHAZ	SHTN1	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
CLEC11A	VWA8	psi-mi:“MI:0914”(association)	0.530
DISC1	AP4M1	psi-mi:“MI:0914”(association)	0.530
LGALS3	PODXL	psi-mi:“MI:0914”(association)	0.530
TAFA4	NRP1	psi-mi:“MI:0914”(association)	0.530
ABRAXAS2	LAMC1	psi-mi:“MI:0914”(association)	0.530
CRP	QSOX1	psi-mi:“MI:0914”(association)	0.530
TGFB1	LAMC1	psi-mi:“MI:0914”(association)	0.530

BioGRID (200): LAMC1 (Affinity Capture-MS), LAMC1 (Affinity Capture-MS), LAMC1 (Affinity Capture-MS), LAMC1 (Affinity Capture-MS), LAMC1 (Affinity Capture-MS), LAMC1 (Affinity Capture-MS), LAMA5 (Co-fractionation), PSMD5 (Co-fractionation), LAMC1 (Two-hybrid), LAMC1 (Reconstituted Complex), LAMC1 (Affinity Capture-MS), LAMC1 (Co-localization), LAMC1 (Affinity Capture-MS), LAMC1 (Affinity Capture-MS), LAMC1 (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: 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

4 interactions.

A	Effect	B	Mechanism
LAMC1	“form complex”	Laminin-9	binding
LAMC1	“form complex”	Laminin-8	binding
LAMC1	“form complex”	Laminin-10	binding
LAMC1	“form complex”	Laminin-1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 132 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
trans-Golgi Network Vesicle Budding	5	14.1×	3e-03
Retinoid metabolism and transport	5	13.8×	3e-03
Signaling by Interleukins	9	6.4×	3e-03
Cytokine Signaling in Immune system	10	4.5×	6e-03
Membrane Trafficking	10	4.1×	9e-03
Neutrophil degranulation	14	3.6×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
ERAD pathway	6	9.4×	8e-03
positive regulation of cell migration	10	5.4×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	199
Likely benign	34
Benign	108

Top pathogenic / likely-pathogenic (0)

SpliceAI

4055 predictions. Top by Δscore:

Variant	Effect	Δscore
1:183103323:CACA:C	acceptor_loss	1.0000
1:183103325:CA:C	acceptor_loss	1.0000
1:183103326:A:AG	acceptor_gain	1.0000
1:183103326:A:C	acceptor_loss	1.0000
1:183103326:AG:A	acceptor_gain	1.0000
1:183103327:G:GT	acceptor_gain	1.0000
1:183103327:GG:G	acceptor_gain	1.0000
1:183103327:GGA:G	acceptor_gain	1.0000
1:183103327:GGAAA:G	acceptor_gain	1.0000
1:183103589:G:GT	donor_gain	1.0000
1:183108263:T:TA	acceptor_gain	1.0000
1:183108402:GGCAG:G	donor_gain	1.0000
1:183108403:GCAGG:G	donor_gain	1.0000
1:183108406:GGT:G	donor_loss	1.0000
1:183108407:G:GA	donor_loss	1.0000
1:183108407:G:GG	donor_gain	1.0000
1:183108408:T:A	donor_loss	1.0000
1:183110634:A:T	donor_gain	1.0000
1:183110653:GC:G	donor_gain	1.0000
1:183114525:T:A	acceptor_gain	1.0000
1:183114529:A:AG	acceptor_gain	1.0000
1:183114529:AGCCT:A	acceptor_gain	1.0000
1:183114530:G:GA	acceptor_gain	1.0000
1:183114530:GC:G	acceptor_gain	1.0000
1:183114530:GCCT:G	acceptor_gain	1.0000
1:183114530:GCCTG:G	acceptor_gain	1.0000
1:183114716:GTGG:G	donor_gain	1.0000
1:183114718:GG:G	donor_gain	1.0000
1:183114719:GG:G	donor_gain	1.0000
1:183114719:GGTAA:G	donor_loss	1.0000

AlphaMissense

10686 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:183023876:T:C	F54L	1.000
1:183023877:T:G	F54C	1.000
1:183023878:C:A	F54L	1.000
1:183023878:C:G	F54L	1.000
1:183023990:T:A	C92S	1.000
1:183023991:G:C	C92S	1.000
1:183024068:T:A	W118R	1.000
1:183024068:T:C	W118R	1.000
1:183024070:G:C	W118C	1.000
1:183024070:G:T	W118C	1.000
1:183024074:A:C	S120R	1.000
1:183024076:C:A	S120R	1.000
1:183024076:C:G	S120R	1.000
1:183103522:T:A	C205S	1.000
1:183103522:T:C	C205R	1.000
1:183103523:G:C	C205S	1.000
1:183103524:T:G	C205W	1.000
1:183108327:T:C	F259L	1.000
1:183108328:T:G	F259C	1.000
1:183108329:T:A	F259L	1.000
1:183108329:T:G	F259L	1.000
1:183108343:T:G	F264C	1.000
1:183110495:T:A	C288S	1.000
1:183110496:G:C	C288S	1.000
1:183110497:T:G	C288W	1.000
1:183110580:G:A	C316Y	1.000
1:183110580:G:T	C316F	1.000
1:183110581:T:G	C316W	1.000
1:183110617:G:C	W328C	1.000
1:183110617:G:T	W328C	1.000

dbSNP variants (sampled 300 via entrez): RS1000000878 (1:183089634 A>C), RS1000017980 (1:183130717 A>G), RS1000042805 (1:183051376 G>A,C), RS1000051368 (1:183094597 A>G), RS1000067068 (1:183048559 C>G), RS1000069801 (1:183089944 A>T), RS1000101742 (1:183095035 G>A), RS1000153821 (1:183118871 T>A,C,G), RS1000184144 (1:183095810 A>C), RS1000185235 (1:183054685 A>G), RS1000185877 (1:183075543 T>A), RS1000189307 (1:183028315 A>G,T), RS1000232346 (1:183031463 C>G,T), RS1000254042 (1:183068766 C>T), RS1000275728 (1:183119149 G>A)

Disease associations

OMIM: gene MIM:150290 | disease phenotypes: MIM:194200

GenCC curated gene-disease

Mondo (1): Wolff-Parkinson-White syndrome (MONDO:0008685)

Orphanet (1): NON RARE IN EUROPE: Wolff-Parkinson-White syndrome (Orphanet:907)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0001716	Wolff-Parkinson-White syndrome

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST001787_7	Colorectal cancer	9.000000e-08
GCST002463_8	Systemic lupus erythematosus	5.000000e-06
GCST002595_11	Clozapine-induced agranulocytosis	1.000000e-06
GCST003743_1	Hypertriglyceridemia	1.000000e-06
GCST003743_6	Hypertriglyceridemia	2.000000e-07
GCST004217_3	Fuchs’s corneal dystrophy	7.000000e-16
GCST006627_64	Diastolic blood pressure	1.000000e-09
GCST007856_85	Colorectal cancer or advanced adenoma	2.000000e-16
GCST008839_70	Height	1.000000e-09
GCST010241_407	Apolipoprotein A1 levels	2.000000e-10
GCST010242_79	HDL cholesterol levels	2.000000e-08
GCST011741_66	LDL cholesterol levels in HIV infection	4.000000e-06
GCST90000025_785	Appendicular lean mass	1.000000e-24
GCST90002384_18	Hemoglobin	2.000000e-10
GCST90002403_52	Red blood cell count	1.000000e-11

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0006336	diastolic blood pressure
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004980	appendicular lean mass
EFO:0004509	hemoglobin measurement
EFO:0004305	erythrocyte count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D014927	Wolff-Parkinson-White Syndrome	C14.280.067.780.977; C14.280.123.750.977; C16.131.240.400.980

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

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation, increases expression	4
Tobacco Smoke Pollution	affects expression, increases expression	3
Valproic Acid	affects expression, increases expression	3
sulindac sulfide	decreases expression, increases expression	2
Copper	affects binding, increases expression	2
Doxorubicin	affects expression, increases expression	2
Endosulfan	decreases expression, increases expression	2
Dihydrotestosterone	increases expression	2
Tretinoin	increases expression, decreases expression	2
Cadmium Chloride	increases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
TL8-506	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
deoxynivalenol	decreases expression	1
trichostatin A	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
16 alpha-ethyl-21-hydroxy-19-nor-4-pregnene-3,20-dione	decreases expression	1
potassium chromate(VI)	decreases expression	1
nickel sulfate	decreases expression	1
tamibarotene	decreases expression	1
CGP 52608	affects binding, increases reaction	1
chloropicrin	decreases expression	1
U 0126	affects reaction, affects expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression	1
bisphenol B	increases expression	1
bisphenol S	increases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects secretion	1

Cellosaurus cell lines

6 cell lines: 4 transformed cell line, 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7TD	Ubigene A-549 LAMC1 KO	Cancer cell line	Male
CVCL_D8P1	Ubigene HCT 116 LAMC1 KO	Cancer cell line	Male
CVCL_RY69	HEK293 rLN10	Transformed cell line	Female
CVCL_RY70	HEK293 rLN10_hNid1	Transformed cell line	Female
CVCL_RY71	HEK293 rLN8	Transformed cell line	Female
CVCL_VN83	HEK293 rLN10_hEcad	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00251121	Not specified	COMPLETED	Routine Mini-invasive Electrophysiology Study for Patients Feeling Tachycardia, With a Negative Holter ECG
NCT00873470	Not specified	TERMINATED	Wolff-Parkinson-White Syndrome Anterograde Refractory Period of Accessory Duct
NCT03207373	Not specified	TERMINATED	Stress ECG Test for the Evaluation of the Risk of Sudden Cardiac Death in a Paediatric Cohort With WPW Pattern
NCT03301935	Not specified	COMPLETED	Risk Assessment in Patients With Symptomatic- and Asymptomatic Preexcitation
NCT03816033	Not specified	UNKNOWN	Cryotherapy Versus Radiofrequency Catheter Ablation Research Program
NCT04106622	Not specified	UNKNOWN	Accessory Pathway Antegrade Effective Refractory Period Among WPW Patients: the Risk in Relation to the Location
NCT06349109	Not specified	COMPLETED	Physical Activity in Children With Wolff-Parkinson-White Syndrome
NCT07435181	Not specified	NOT_YET_RECRUITING	Comparative Outcomes of Radiofrequency Ablation of Concealed and Manifest Accessory Pathways: a Single Center, Retrospective Observational Study