LAMC3

Summary

LAMC3 (laminin subunit gamma 3, HGNC:6494) is a protein-coding gene on chromosome 9q34.12, encoding Laminin subunit gamma-3 (Q9Y6N6). 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 are composed of 3 non identical chains: laminin alpha, beta and gamma (formerly A, B1, and B2, respectively) and they form a cruciform structure consisting of 3 short arms, each formed by a different chain, and a long arm composed of all 3 chains. Each laminin chain is a multidomain protein encoded by a distinct gene. Several isoforms of each chain have been described. Different alpha, beta and gamma chain isomers combine to give rise to different heterotrimeric laminin isoforms which are designated by Arabic numerals in the order of their discovery, i.e. alpha1beta1gamma1 heterotrimer is laminin 1. The biological functions of the different chains and trimer molecules are largely unknown, but some of the chains have been shown to differ with respect to their tissue distribution, presumably reflecting diverse functions in vivo. This gene encodes the gamma chain isoform laminin, gamma 3. The gamma 3 chain is most similar to the gamma 1 chain, and contains all the 6 domains expected of the gamma chain. It is a component of laminin 12. The gamma 3 chain is broadly expressed in skin, heart, lung, and the reproductive tracts. In skin, it is seen within the basement membrane of the dermal-epidermal junction at points of nerve penetration. Gamma 3 is also a prominent element of the apical surface of ciliated epithelial cells of lung, oviduct, epididymis, ductus deferens, and seminiferous tubules. The distribution of gamma 3-containing laminins along ciliated epithelial surfaces suggests that the apical laminins are important in the morphogenesis and structural stability of the ciliated processes of these cells.

Source: NCBI Gene 10319 — RefSeq curated summary.

At a glance

• Gene–disease (curated): occipital pachygyria and polymicrogyria (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 7
• Clinical variants (ClinVar): 1,836 total — 70 pathogenic, 38 likely-pathogenic
• Phenotypes (HPO): 9
• Druggable target: yes
• MANE Select transcript: NM_006059

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6494
Approved symbol	LAMC3
Name	laminin subunit gamma 3
Location	9q34.12
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp434E202
Ensembl gene	ENSG00000050555
Ensembl biotype	protein_coding
OMIM	604349
Entrez	10319

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 9 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000355452, ENST00000361069, ENST00000462567, ENST00000678544, ENST00000678758, ENST00000679272, ENST00000868026, ENST00000940484, ENST00000955223, ENST00000955224, ENST00000955225

RefSeq mRNA: 1 — MANE Select: NM_006059 NM_006059

CCDS: CCDS6938

Canonical transcript exons

ENST00000361069 — 28 exons

Exon	Start	End
ENSE00000732606	131073245	131073321
ENSE00000732612	131085524	131085723
ENSE00000868164	131071484	131071625
ENSE00000868166	131079149	131079298
ENSE00000896096	131061035	131061223
ENSE00000896097	131066960	131067205
ENSE00001095078	131068078	131068231
ENSE00001141238	131077187	131077334
ENSE00001141244	131075831	131075965
ENSE00001141256	131072630	131072835
ENSE00001141268	131069672	131069850
ENSE00001141273	131068908	131069050
ENSE00001141297	131056929	131057147
ENSE00001141305	131052850	131052965
ENSE00001141311	131052491	131052683
ENSE00001141317	131049020	131049130
ENSE00001141322	131045524	131045660
ENSE00001369998	131082059	131082161
ENSE00001554244	131091537	131094473
ENSE00001865686	131009174	131009587
ENSE00003475762	131087718	131087817
ENSE00003515571	131038864	131039052
ENSE00003521348	131041637	131041735
ENSE00003527174	131032045	131032175
ENSE00003622077	131039131	131039248
ENSE00003647272	131026285	131026589
ENSE00003661972	131087476	131087622
ENSE00003683355	131036166	131036332

Expression profiles

Bgee: expression breadth ubiquitous, 184 present calls, max score 94.30.

FANTOM5 (CAGE): breadth broad, TPM avg 2.7020 / max 133.5212, expressed in 502 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
99047	2.7020	502

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endocervix	UBERON:0000458	94.30	gold quality
metanephros cortex	UBERON:0010533	93.87	gold quality
right lung	UBERON:0002167	93.32	gold quality
left testis	UBERON:0004533	92.20	gold quality
upper lobe of left lung	UBERON:0008952	91.57	gold quality
adenohypophysis	UBERON:0002196	90.85	gold quality
right adrenal gland cortex	UBERON:0035827	90.79	gold quality
ectocervix	UBERON:0012249	90.51	gold quality
right testis	UBERON:0004534	90.49	gold quality
upper lobe of lung	UBERON:0008948	90.33	gold quality
left adrenal gland	UBERON:0001234	89.18	gold quality
testis	UBERON:0000473	89.08	gold quality
right adrenal gland	UBERON:0001233	89.08	gold quality
left adrenal gland cortex	UBERON:0035825	88.87	gold quality
adrenal cortex	UBERON:0001235	88.64	gold quality
spleen	UBERON:0002106	87.86	gold quality
pituitary gland	UBERON:0000007	87.38	gold quality
placenta	UBERON:0001987	87.29	gold quality
skin of leg	UBERON:0001511	86.94	gold quality
adrenal gland	UBERON:0002369	86.57	gold quality
skin of abdomen	UBERON:0001416	84.67	gold quality
zone of skin	UBERON:0000014	83.25	gold quality
vagina	UBERON:0000996	80.26	gold quality
urinary bladder	UBERON:0001255	79.92	gold quality
right lobe of liver	UBERON:0001114	79.67	gold quality
lung	UBERON:0002048	79.66	gold quality
adult mammalian kidney	UBERON:0000082	78.70	gold quality
gall bladder	UBERON:0002110	78.55	gold quality
uterine cervix	UBERON:0000002	78.00	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.19	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	11.13
E-ANND-3	yes	5.97
E-MTAB-6678	no	3.68

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

43 targeting LAMC3, 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-6867-5P	100.00	82.21	3464
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-567	99.63	68.57	1219
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-1324	99.46	66.57	1302
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-3911	99.38	66.95	1087
HSA-MIR-3692-5P	99.29	67.04	1421
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-6071	99.16	67.77	1780
HSA-MIR-7160-5P	99.11	67.17	2207
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-331-3P	98.76	64.91	793
HSA-MIR-330-5P	98.73	67.63	1788

Literature-anchored findings (GeneRIF, showing 10)

• 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)
• Recessive LAMC3 mutations cause malformations of occipital cortical development. (PMID:21572413)
• These data suggest that beta2 and gamma3-containing laminins play an important dose-dependent role in development of the cortical pial basement membrane (PMID:22961762)
• We found statistically significant association with AAO for three genes (WRN, NTN4 and LAMC3) with common associated variants. (PMID:26394601)
• LAMC3 gene variation is associated with oral cavity and pharyngeal cancer. (PMID:27749845)
• Study reports a novel mutation in LAMC3 associated with generalized polymicrogyria of the cortex and epilepsy. Study identified a homozygous nonsense mutation in LAMC3: c.3190C>T (p.Gln1064*). (PMID:29247375)
• LAMC3 mutation causes structural and functional impairments in visual attention networks. (PMID:29626609)
• These data demonstrate a unique temporal and spatial expression for laminins and reveal a novel role for laminin gamma3 during human retinogenesis. (PMID:29795281)
• [Relationships between decreased LAMC3 and poor prognosis in ovarian cancer]. (PMID:34304441)
• Novel LAMC3 pathogenic variant enriched in Finnish population causes malformations of cortical development and severe epilepsy. (PMID:38758065)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Lamc3	ENSMUSG00000026840
rattus_norvegicus	Lamc3	ENSRNOG00000059507

Paralogs (27): USH2A (ENSG00000042781), 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), LAMB3 (ENSG00000196878), TMEFF1 (ENSG00000241697)

Protein

Protein identifiers

Laminin subunit gamma-3 — Q9Y6N6 (reviewed: Q9Y6N6)

Alternative names: Laminin-12 subunit gamma, Laminin-14 subunit gamma, Laminin-15 subunit gamma

All UniProt accessions (4): A0A7I2V3S4, A0A7I2YQP4, H7BY04, Q9Y6N6

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. Gamma-3 is a subunit of laminin-12 (laminin-213), laminin-14 (laminin-423) and laminin-15 (laminin-523).

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

Tissue specificity. Broadly expressed in: skin, heart, lung, and the reproductive tracts.

Disease relevance. Cortical malformations occipital (OCCM) [MIM:614115] A disease in which affected individuals develop seizures, sometimes associated with transient visual changes. Brain MRI shows both pachygyria and polymicrogyria restricted to the lateral occipital lobes. 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 IV is globular.

RefSeq proteins (1): NP_006050* (*=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 (85 total): disulfide bond 40, domain 14, glycosylation site 8, sequence conflict 8, sequence variant 6, coiled-coil region 4, region of interest 2, signal peptide 1, chain 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y6N6-F1	75.23	0.15

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 (40): 271–280, 273–290, 292–301, 304–324, 327–336, 329–352, 355–364, 367–380, 383–395, 385–401, 403–412, 415–427, 430–441, 432–448, 450–459, 462–477, 707–715, 709–722, 724–733, 736–752 …

Glycosylation sites (8): 87, 119, 295, 328, 631, 837, 980, 1185

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-3000157	Laminin interactions
R-HSA-3000171	Non-integrin membrane-ECM interactions
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-162582	Signal Transduction
R-HSA-6806834	Signaling by MET
R-HSA-8875878	MET promotes cell motility
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases

MSigDB gene sets: 130 (showing top): GOBP_GLIAL_CELL_DEVELOPMENT, GOBP_NEUROGENESIS, KEGG_PATHWAYS_IN_CANCER, GOMF_EXTRACELLULAR_MATRIX_STRUCTURAL_CONSTITUENT, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, GOBP_ASTROCYTE_DIFFERENTIATION, GOBP_SUBSTRATE_ADHESION_DEPENDENT_CELL_SPREADING, GOBP_SENSORY_PERCEPTION, GOBP_SENSORY_ORGAN_DEVELOPMENT, GOCC_BASEMENT_MEMBRANE, GOBP_GLIAL_CELL_DIFFERENTIATION, GOBP_CELL_SUBSTRATE_ADHESION, GOBP_RETINA_DEVELOPMENT_IN_CAMERA_TYPE_EYE, GOBP_ASTROCYTE_DEVELOPMENT, MULLIGHAN_MLL_SIGNATURE_2_DN

GO Biological Process (6): cell morphogenesis (GO:0000902), cell adhesion (GO:0007155), visual perception (GO:0007601), astrocyte development (GO:0014002), radial glial cell differentiation (GO:0060019), retina development in camera-type eye (GO:0060041)

GO Molecular Function (1): structural molecule activity (GO:0005198)

GO Cellular Component (4): extracellular region (GO:0005576), basement membrane (GO:0005604), membrane (GO:0016020), extracellular matrix (GO:0031012)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Extracellular matrix organization	2
MET promotes cell motility	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
cellular anatomical structure	2
anatomical structure morphogenesis	1
cellular process	1
sensory perception of light stimulus	1
glial cell development	1
astrocyte differentiation	1
glial cell differentiation	1
camera-type eye development	1
anatomical structure development	1
molecular_function	1
extracellular matrix	1
external encapsulating structure	1

Protein interactions and networks

STRING

1384 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LAMC3	CDC6	Q99741	888
LAMC3	CDT1	Q9H211	849
LAMC3	LAMA4	Q16363	572
LAMC3	MCM3	P25205	572
LAMC3	LAMA3	Q16787	542
LAMC3	RELN	P78509	539
LAMC3	ITGB8	P26012	530
LAMC3	ITGA10	O75578	529
LAMC3	ITGB4	P16144	515
LAMC3	ITGA5	P08648	488
LAMC3	IBSP	P21815	482
LAMC3	ORC5	O43913	460
LAMC3	ORC4	O43929	447
LAMC3	BGLAP	P02818	447
LAMC3	ORC6	Q9Y5N6	446

IntAct

38 interactions, top by confidence:

A	B	Type	Score
SGF29	NDC80	psi-mi:“MI:0914”(association)	0.840
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
TGFB1	LAMC1	psi-mi:“MI:0914”(association)	0.530
LAMC3	AATF	psi-mi:“MI:0915”(physical association)	0.400
LAMC3	CHD4	psi-mi:“MI:0915”(physical association)	0.400
LAMC3	PRKDC	psi-mi:“MI:0915”(physical association)	0.400
NS	LAMC3	psi-mi:“MI:0915”(physical association)	0.370
NS2	LAMC3	psi-mi:“MI:0915”(physical association)	0.370
LAMC3	NS	psi-mi:“MI:0915”(physical association)	0.370
NR1H2	LAMC3	psi-mi:“MI:0915”(physical association)	0.370
LAMC3	RPL35	psi-mi:“MI:0915”(physical association)	0.370
LAMC3	ZNF160	psi-mi:“MI:0915”(physical association)	0.370
ANXA5	LAMC3	psi-mi:“MI:0915”(physical association)	0.370
LAMC3	CFB	psi-mi:“MI:0915”(physical association)	0.370
CRP	LAMC3	psi-mi:“MI:0915”(physical association)	0.370
CSNK2A2	LAMC3	psi-mi:“MI:0915”(physical association)	0.370
CYP2E1	LAMC3	psi-mi:“MI:0915”(physical association)	0.370
HP	LAMC3	psi-mi:“MI:0915”(physical association)	0.370
LAMC3	LGMN	psi-mi:“MI:0915”(physical association)	0.370
TF	LAMC3	psi-mi:“MI:0915”(physical association)	0.370
FRAT1	LAMC3	psi-mi:“MI:0915”(physical association)	0.370
LAMC3	KIF1C	psi-mi:“MI:0915”(physical association)	0.370
POT1	LAMC3	psi-mi:“MI:0915”(physical association)	0.370
LAMC3	SLC43A3	psi-mi:“MI:0915”(physical association)	0.370
EPB41L4B	LAMC3	psi-mi:“MI:0915”(physical association)	0.370
LAMC3	CWC25	psi-mi:“MI:0915”(physical association)	0.370
LAMC3	PELI2	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (44): LAMC3 (Proximity Label-MS), LAMC3 (Affinity Capture-RNA), LAMC3 (Affinity Capture-MS), LAMC3 (Proximity Label-MS), LAMC3 (Proximity Label-MS), LAMC3 (Proximity Label-MS), TMTC3 (Affinity Capture-MS), TXLNA (Affinity Capture-MS), TGFB1 (Affinity Capture-MS), LAMC3 (Affinity Capture-MS), NID1 (Affinity Capture-MS), CCDC101 (Affinity Capture-MS), LAMB1 (Affinity Capture-MS), LAMC3 (Affinity Capture-MS), LAMC3 (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

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 38 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
Platelet degranulation	5	14.2×	5e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

1836 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	70
Likely pathogenic	38
Uncertain significance	778
Likely benign	705
Benign	133

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1074722	NM_006059.4(LAMC3):c.3721C>T (p.Gln1241Ter)	Pathogenic
1324651	NM_006059.4(LAMC3):c.976+1G>A	Pathogenic
1359127	NM_006059.4(LAMC3):c.223C>T (p.Gln75Ter)	Pathogenic
1365119	NM_006059.4(LAMC3):c.2480del (p.Leu827fs)	Pathogenic
1371535	NM_006059.4(LAMC3):c.1282A>T (p.Arg428Ter)	Pathogenic
1376853	NM_006059.4(LAMC3):c.332dup (p.Val112fs)	Pathogenic
1404975	NM_006059.4(LAMC3):c.3438del (p.Ser1147fs)	Pathogenic
1417707	NM_006059.4(LAMC3):c.513C>G (p.Tyr171Ter)	Pathogenic
1421192	NM_006059.4(LAMC3):c.1698dup (p.Gly567fs)	Pathogenic
1426114	NM_006059.4(LAMC3):c.3953del (p.Leu1318fs)	Pathogenic
1426198	NM_006059.4(LAMC3):c.3051C>A (p.Tyr1017Ter)	Pathogenic
1429559	NM_006059.4(LAMC3):c.2382dup (p.Gly795fs)	Pathogenic
1451732	NM_006059.4(LAMC3):c.317dup (p.Ser107fs)	Pathogenic
1452042	NM_006059.4(LAMC3):c.877C>T (p.Gln293Ter)	Pathogenic
1454553	NM_006059.4(LAMC3):c.2336del (p.Pro779fs)	Pathogenic
1456144	NC_000009.11:g.(?133878071)(133884691_?)del	Pathogenic
1456570	NM_006059.4(LAMC3):c.2302G>T (p.Glu768Ter)	Pathogenic
1456928	NM_006059.4(LAMC3):c.2090del (p.Gln697fs)	Pathogenic
1457800	NC_000009.11:g.(?133952554)(133952741_?)del	Pathogenic
1458997	NM_006059.4(LAMC3):c.1470_1471dup (p.Ser491fs)	Pathogenic
1460008	NM_006059.4(LAMC3):c.2127T>A (p.Cys709Ter)	Pathogenic
1895715	NM_006059.4(LAMC3):c.1720C>T (p.Gln574Ter)	Pathogenic
1908117	NM_006059.4(LAMC3):c.1064del (p.Cys355fs)	Pathogenic
1908192	NM_006059.4(LAMC3):c.1553dup (p.Ser519fs)	Pathogenic
1935953	NM_006059.4(LAMC3):c.2242C>T (p.Gln748Ter)	Pathogenic
1938563	NM_006059.4(LAMC3):c.1828C>T (p.Gln610Ter)	Pathogenic
1944772	NC_000009.12:g.131066961del	Pathogenic
1962286	NM_006059.4(LAMC3):c.345del (p.Thr116fs)	Pathogenic
1993914	NM_006059.4(LAMC3):c.2280_2284del (p.Gln760fs)	Pathogenic
2011052	NM_006059.4(LAMC3):c.1609G>T (p.Glu537Ter)	Pathogenic

SpliceAI

5559 predictions. Top by Δscore:

Variant	Effect	Δscore
9:131009585:TAGG:T	donor_loss	1.0000
9:131009586:AGGT:A	donor_loss	1.0000
9:131009588:GTA:G	donor_loss	1.0000
9:131009589:T:A	donor_loss	1.0000
9:131026573:A:T	donor_gain	1.0000
9:131026596:G:T	donor_gain	1.0000
9:131036254:GACT:G	donor_gain	1.0000
9:131036331:GC:G	donor_gain	1.0000
9:131036333:G:GG	donor_gain	1.0000
9:131038862:A:AG	acceptor_gain	1.0000
9:131038863:G:GG	acceptor_gain	1.0000
9:131038863:GCCT:G	acceptor_gain	1.0000
9:131039052:GGTG:G	donor_loss	1.0000
9:131039053:GT:G	donor_loss	1.0000
9:131039054:T:A	donor_loss	1.0000
9:131052848:A:AG	acceptor_gain	1.0000
9:131052849:G:GG	acceptor_gain	1.0000
9:131052849:GCCT:G	acceptor_gain	1.0000
9:131052970:G:GG	donor_gain	1.0000
9:131071472:T:A	acceptor_gain	1.0000
9:131071479:TCCA:T	acceptor_loss	1.0000
9:131071482:A:AG	acceptor_gain	1.0000
9:131071482:AG:A	acceptor_gain	1.0000
9:131071482:AGGCA:A	acceptor_loss	1.0000
9:131071483:G:GA	acceptor_gain	1.0000
9:131071483:GG:G	acceptor_gain	1.0000
9:131071483:GGC:G	acceptor_gain	1.0000
9:131071483:GGCA:G	acceptor_gain	1.0000
9:131071621:TCCAG:T	donor_loss	1.0000
9:131071622:CCAG:C	donor_loss	1.0000

AlphaMissense

10278 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:131009330:T:G	F39C	0.999
9:131009521:T:A	W103R	0.999
9:131009521:T:C	W103R	0.999
9:131009523:G:C	W103C	0.999
9:131009523:G:T	W103C	0.999
9:131009527:A:C	S105R	0.999
9:131009529:C:A	S105R	0.999
9:131009529:C:G	S105R	0.999
9:131026336:C:A	P142H	0.999
9:131026479:T:A	C190S	0.998
9:131026480:G:C	C190S	0.998
9:131032050:G:C	W228C	0.998
9:131032050:G:T	W228C	0.998
9:131032097:T:G	F244C	0.998
9:131009329:T:C	F39L	0.997
9:131009331:C:A	F39L	0.997
9:131009331:C:G	F39L	0.997
9:131009375:G:A	C54Y	0.997
9:131009443:T:A	C77S	0.997
9:131009444:G:C	C77S	0.997
9:131026315:T:C	L135P	0.997
9:131026320:T:C	F137L	0.997
9:131026322:C:A	F137L	0.997
9:131026322:C:G	F137L	0.997
9:131026401:A:C	S164R	0.997
9:131026403:C:A	S164R	0.997
9:131026403:C:G	S164R	0.997
9:131026479:T:C	C190R	0.997
9:131026480:G:A	C190Y	0.997
9:131026481:C:G	C190W	0.997

dbSNP variants (sampled 300 via entrez): RS1000027321 (9:131032634 T>C), RS1000035998 (9:131074783 A>T), RS1000123834 (9:131033924 T>C), RS1000189575 (9:131032995 C>G,T), RS1000218812 (9:131047901 T>C), RS1000248811 (9:131029573 A>G), RS1000389085 (9:131078094 C>T), RS1000400944 (9:131059139 T>A,C), RS1000413276 (9:131056772 A>C), RS1000420391 (9:131021916 G>T), RS1000428331 (9:131074961 C>T), RS1000497365 (9:131034148 G>A,C), RS1000525577 (9:131051434 G>A), RS1000598343 (9:131027750 G>A,T), RS1000634575 (9:131067590 G>C)

Disease associations

OMIM: gene MIM:604349 | disease phenotypes: MIM:614115, MIM:604169

GenCC curated gene-disease

Disease	Classification	Inheritance
occipital pachygyria and polymicrogyria	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Disputed	AD

Mondo (3): occipital pachygyria and polymicrogyria (MONDO:0013583), left ventricular noncompaction (MONDO:0018901), intellectual disability (MONDO:0001071)

Orphanet (3): Occipital pachygyria and polymicrogyria (Orphanet:280640), Left ventricular noncompaction (Orphanet:54260), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

9 total (9 of 9 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000572	Visual loss
HP:0001263	Global developmental delay
HP:0001302	Pachygyria
HP:0002069	Bilateral tonic-clonic seizure
HP:0002126	Polymicrogyria
HP:0002353	EEG abnormality
HP:0003621	Juvenile onset
HP:0032909	Focal impaired awareness automatism seizure

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST003857_5	Oral cavity and pharyngeal cancer	3.000000e-07
GCST003858_5	Oral cavity cancer	2.000000e-08
GCST004368_6	Endometriosis	6.000000e-07
GCST004370_10	Deep ovarian and/or rectovaginal disease with dense adhesions	1.000000e-06
GCST005441_5	Alcohol consumption (max-drinks)	2.000000e-06
GCST008667_2	Smoking status (heavy vs never)	4.000000e-07
GCST009304_8	Degraded stimulus continuous performance test score	4.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006527	smoking status measurement
EFO:0007636	attention function measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539

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

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation, decreases expression	2
entinostat	increases expression, affects cotreatment	2
Benzo(a)pyrene	affects methylation, increases methylation	2
Valproic Acid	affects expression, increases methylation	2
peracetylated N-azidoacetylmannosamine	decreases expression	1
4-oxoretinoic acid	increases expression	1
2,4,6-tribromophenol	increases expression	1
decabromobiphenyl ether	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
sodium arsenite	affects methylation	1
tetrabromobisphenol A	increases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	increases methylation	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
nutlin 3	increases expression, affects cotreatment	1
ICG 001	increases expression	1
abrine	decreases expression	1
quinocetone	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	increases expression	1
bisphenol S	decreases methylation	1
jinfukang	affects cotreatment, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Alitretinoin	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_D7TE	Ubigene A-549 LAMC3 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT01470014	Not specified	COMPLETED	Cardiac Computed Tomography: Characteristics of Isolated Left Ventricular Non-compaction
NCT01481298	Not specified	COMPLETED	Value of Cardiac Magnetic Resonance (CMR) Derived Parameters for Diagnosing Left Ventricular Non-compaction Cardiomyopathy
NCT02432092	Not specified	RECRUITING	Pediatric Cardiomyopathy Mutation Analysis
NCT02568072	Not specified	COMPLETED	Training-induced Increased Left Ventricular Trabeculation
NCT03572569	Not specified	UNKNOWN	Risk Stratification in Children and Adolescents With Primary Cardiomyopathy
NCT06024759	Not specified	RECRUITING	Predictors of Risk in Left Ventricular Non-Compaction
NCT06607471	Not specified	RECRUITING	Multimodal and Multidisciplinary Approach to Optimize Diagnostic, Prognostic, and Therapeutic Management of Patients with Non-ischemic Cardiomyopathies and Arrhythmogenic-inflammatory Phenotypes: a Multicenter, Observational, Retrospective and Prospective Registry Study.
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients