LAMB4

Summary

LAMB4 (laminin subunit beta 4, HGNC:6491) is a protein-coding gene on chromosome 7q31.1, encoding Laminin subunit beta-4 (A4D0S4). 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.

Predicted to be involved in cell adhesion. Predicted to be located in basement membrane and extracellular region.

Source: NCBI Gene 22798 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 286 total
• Druggable target: yes
• MANE Select transcript: NM_007356

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6491
Approved symbol	LAMB4
Name	laminin subunit beta 4
Location	7q31.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000091128
Ensembl biotype	protein_coding
OMIM	616380
Entrez	22798

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 4 protein_coding, 2 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000205386, ENST00000388781, ENST00000418464, ENST00000422975, ENST00000471677, ENST00000475469, ENST00000475572, ENST00000483484

RefSeq mRNA: 4 — MANE Select: NM_007356 NM_001318046, NM_001318047, NM_001318048, NM_007356

CCDS: CCDS34732, CCDS83218

Canonical transcript exons

ENST00000388781 — 34 exons

Exon	Start	End
ENSE00001025938	108023553	108024178
ENSE00003484546	108098403	108098582
ENSE00003490612	108079601	108079786
ENSE00003523139	108076944	108077064
ENSE00003530326	108066369	108066600
ENSE00003533952	108105817	108106031
ENSE00003540412	108078201	108078316
ENSE00003542251	108095228	108095337
ENSE00003542982	108103044	108103232
ENSE00003551878	108034208	108034346
ENSE00003561949	108091626	108091776
ENSE00003567363	108029043	108029196
ENSE00003571128	108104499	108104619
ENSE00003571613	108107631	108107819
ENSE00003572730	108116004	108116161
ENSE00003574234	108068016	108068159
ENSE00003582151	108106509	108106572
ENSE00003610466	108069708	108069885
ENSE00003625001	108109171	108109244
ENSE00003633117	108043752	108043896
ENSE00003635584	108111811	108111946
ENSE00003638876	108065762	108065919
ENSE00003642971	108063761	108063985
ENSE00003680944	108037388	108037595
ENSE00003689752	108092337	108092416
ENSE00003844333	108130306	108130361
ENSE00003888976	108123131	108123197
ENSE00003890536	108062774	108062994
ENSE00003891149	108047908	108048111
ENSE00003892366	108030806	108030979
ENSE00003893462	108057832	108057928
ENSE00003894868	108049326	108049531
ENSE00003895450	108052097	108052257
ENSE00003895755	108055632	108056007

Expression profiles

Bgee: expression breadth ubiquitous, 166 present calls, max score 94.63.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3914 / max 141.7670, expressed in 35 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
85651	0.3914	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skin of abdomen	UBERON:0001416	94.63	gold quality
skin of leg	UBERON:0001511	93.70	gold quality
zone of skin	UBERON:0000014	91.46	gold quality
skin of hip	UBERON:0001554	86.63	gold quality
upper leg skin	UBERON:0004262	83.93	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.80	gold quality
buccal mucosa cell	CL:0002336	77.77	silver quality
nipple	UBERON:0002030	74.85	gold quality
upper arm skin	UBERON:0004263	72.92	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	71.51	gold quality
esophagus mucosa	UBERON:0002469	70.84	gold quality
small intestine Peyer’s patch	UBERON:0003454	66.91	gold quality
lower esophagus mucosa	UBERON:0035834	65.47	gold quality
oral cavity	UBERON:0000167	64.98	gold quality
stromal cell of endometrium	CL:0002255	64.45	gold quality
esophagus	UBERON:0001043	64.23	gold quality
small intestine	UBERON:0002108	63.97	gold quality
metanephros cortex	UBERON:0010533	62.26	gold quality
sperm	CL:0000019	61.81	silver quality
male germ cell	CL:0000015	61.04	silver quality
placenta	UBERON:0001987	60.09	gold quality
Brodmann (1909) area 10	UBERON:0013541	59.85	gold quality
adult mammalian kidney	UBERON:0000082	58.99	gold quality
jejunal mucosa	UBERON:0000399	58.54	gold quality
omental fat pad	UBERON:0010414	58.45	gold quality
peritoneum	UBERON:0002358	58.44	gold quality
islet of Langerhans	UBERON:0000006	57.97	gold quality
adipose tissue of abdominal region	UBERON:0007808	57.48	gold quality
right lobe of thyroid gland	UBERON:0001119	57.45	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	57.36	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-2	yes	1622.08
E-ANND-3	yes	9.03

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

40 targeting LAMB4, 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-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-8076	99.78	68.52	1170
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-513A-3P	99.39	70.63	3620
HSA-MIR-513C-3P	99.39	70.63	3620
HSA-MIR-6507-5P	99.36	70.46	2524
HSA-MIR-4311	99.31	70.47	3041
HSA-MIR-580-5P	99.28	70.94	1776
HSA-MIR-892C-5P	99.16	70.56	2116
HSA-MIR-3125	99.14	68.49	2269
HSA-MIR-3606-3P	99.11	69.84	3254
HSA-MIR-3916	98.99	68.04	2155
HSA-MIR-6859-5P	98.99	68.07	2049

Literature-anchored findings (GeneRIF, showing 3)

• Loss of LAMB4 expression was identified in 17-32% of the GC and CRC. Of note, the loss expression was more common in the cancers with LAMB4 mutation or those with MSI-H. (PMID:25257191)
• We identified a rare single nucleotide variant in the laminin beta 4 gene (LAMB4) that segregated with familial diverticulitis in a dominant pattern and causes a damaging missense substitution (D435N). Targeted sequencing of LAMB4 in 148 non-familial and unrelated sporadic diverticulitis patients identified two additional rare variants in the gene. (PMID:28595269)
• Laminin beta4 is a constituent of the cutaneous basement membrane zone and additional autoantigen of anti-p200 pemphigoid. (PMID:37992812)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
danio_rerio	lamb4	ENSDARG00000039133

Paralogs (27): USH2A (ENSG00000042781), LAMC3 (ENSG00000050555), LAMA3 (ENSG00000053747), LAMC2 (ENSG00000058085), NTN1 (ENSG00000065320), NTN4 (ENSG00000074527), ATRN (ENSG00000088812), 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 beta-4 — A4D0S4 (reviewed: A4D0S4)

Alternative names: Laminin beta-1-related protein

All UniProt accessions (3): A4D0S4, A0A0C4DG90, C9JMJ0

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.

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

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.

Isoforms (3)

UniProt ID	Names	Canonical?
A4D0S4-1	1	yes
A4D0S4-2	2
A4D0S4-3	3

RefSeq proteins (4): NP_001304975, NP_001304976, NP_001304977, NP_031382* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002049	LE_dom	Domain
IPR008211	Laminin_N	Domain
IPR013015	Laminin_IV_B	Domain
IPR050440	Laminin/Netrin_ECM	Family
IPR056558	LAMB1-4_helical	Domain
IPR056860	LAMB4_dom	Domain
IPR056863	LMN_ATRN_NET-like_EGF	Domain

Pfam: PF00053, PF00055, PF21199, PF23219, PF24973, PF24999

UniProt features (107 total): disulfide bond 53, glycosylation site 16, domain 15, sequence variant 8, splice variant 4, sequence conflict 3, region of interest 3, coiled-coil region 3, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A4D0S4-F1	74.52	0.09

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 (53): 265–274, 267–295, 297–306, 309–329, 332–341, 334–359, 362–371, 374–392, 395–408, 397–423, 425–434, 437–452, 455–468, 457–475, 477–486, 489–503, 506–518, 508–525, 527–536, 769–781 …

Glycosylation sites (16): 169, 229, 246, 1016, 1055, 1223, 1301, 1326, 1333, 1354, 1469, 1517, 1587, 1596, 1609, 1725

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 56 (showing top): KEGG_PATHWAYS_IN_CANCER, GOMF_EXTRACELLULAR_MATRIX_STRUCTURAL_CONSTITUENT, GOBP_SUBSTRATE_ADHESION_DEPENDENT_CELL_SPREADING, GOCC_BASEMENT_MEMBRANE, GOBP_CELL_SUBSTRATE_ADHESION, chr7q31, GOMF_STRUCTURAL_MOLECULE_ACTIVITY, GOCC_LAMININ_COMPLEX, GOCC_EXTERNAL_ENCAPSULATING_STRUCTURE, CBX5_TARGET_GENES, HMGA1_TARGET_GENES, NABA_ECM_GLYCOPROTEINS, RBM34_TARGET_GENES, TFEB_TARGET_GENES, MIR4753_3P

GO Biological Process (1): cell adhesion (GO:0007155)

GO Molecular Function (0):

GO Cellular Component (3): extracellular region (GO:0005576), laminin-121 trimer (GO:0005608), basement membrane (GO:0005604)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular process	1
cellular anatomical structure	1
laminin trimer	1
extracellular matrix	1

Protein interactions and networks

STRING

656 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LAMB4	PIK3CG	P48736	549
LAMB4	ZC3H10	Q96K80	517
LAMB4	CBLN3	Q6UW01	440
LAMB4	NALF1	B1AL88	432
LAMB4	CLEC19A	Q6UXS0	428
LAMB4	PECR	Q9BY49	412
LAMB4	LAMB3	Q13751	363
LAMB4	PLTP	P55058	358
LAMB4	COL4A6	Q14031	358
LAMB4	STAG2	Q8N3U4	357
LAMB4	C1QTNF7	Q9BXJ2	356
LAMB4	VWDE	Q8N2E2	341
LAMB4	DCAF8	Q5TAQ9	334
LAMB4	ZRSR2	Q15696	333
LAMB4	COL24A1	Q17RW2	315

IntAct

2 interactions, top by confidence:

A	B	Type	Score
KCTD13	LAMB4	psi-mi:“MI:0914”(association)	0.350

BioGRID (5): LAMB4 (Co-fractionation), LAMB4 (Affinity Capture-MS), LAMB4 (Affinity Capture-MS), LAMB4 (Protein-peptide), LAMB4 (Affinity Capture-MS)

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

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	235
Likely benign	20
Benign	19

Top pathogenic / likely-pathogenic (0)

SpliceAI

4843 predictions. Top by Δscore:

Variant	Effect	Δscore
7:108037386:A:AC	donor_gain	1.0000
7:108037387:C:CA	donor_gain	1.0000
7:108037387:CT:C	donor_gain	1.0000
7:108037387:CTCA:C	donor_gain	1.0000
7:108037387:CTCAG:C	donor_gain	1.0000
7:108037391:G:C	donor_gain	1.0000
7:108037596:C:CC	acceptor_gain	1.0000
7:108037597:T:C	acceptor_gain	1.0000
7:108043755:A:C	donor_gain	1.0000
7:108043769:A:AC	donor_gain	1.0000
7:108043770:C:CC	donor_gain	1.0000
7:108048109:CACCT:C	acceptor_gain	1.0000
7:108049564:T:TC	acceptor_gain	1.0000
7:108052091:CCTT:C	donor_loss	1.0000
7:108052092:CTTA:C	donor_loss	1.0000
7:108052093:TTACC:T	donor_loss	1.0000
7:108052094:TACC:T	donor_loss	1.0000
7:108052095:AC:A	donor_gain	1.0000
7:108052096:CC:C	donor_gain	1.0000
7:108052141:T:TA	donor_gain	1.0000
7:108052255:CTT:C	acceptor_gain	1.0000
7:108052256:TT:T	acceptor_gain	1.0000
7:108052258:C:CC	acceptor_gain	1.0000
7:108063759:A:AC	donor_gain	1.0000
7:108063760:C:CC	donor_gain	1.0000
7:108063760:CTT:C	donor_gain	1.0000
7:108063855:C:A	donor_gain	1.0000
7:108063984:ACC:A	acceptor_loss	1.0000
7:108063986:C:G	acceptor_loss	1.0000
7:108076942:A:AC	donor_gain	1.0000

AlphaMissense

11640 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:108111824:C:A	W105C	0.975
7:108111824:C:G	W105C	0.975
7:108111826:A:G	W105R	0.972
7:108111826:A:T	W105R	0.972
7:108103112:C:G	C371S	0.967
7:108103113:A:T	C371S	0.967
7:108063805:C:G	C1006S	0.966
7:108063806:A:T	C1006S	0.966
7:108107674:C:G	C183S	0.966
7:108107675:A:T	C183S	0.966
7:108109174:A:C	F133L	0.965
7:108109174:A:T	F133L	0.965
7:108109176:A:G	F133L	0.965
7:108062849:C:A	W1069C	0.958
7:108062849:C:G	W1069C	0.958
7:108063814:C:G	C1003S	0.957
7:108063815:A:T	C1003S	0.957
7:108098462:C:G	C434S	0.956
7:108098463:A:T	C434S	0.956
7:108107814:A:C	F136L	0.954
7:108107814:A:T	F136L	0.954
7:108107816:A:G	F136L	0.954
7:108066476:A:C	F857L	0.953
7:108066476:A:T	F857L	0.953
7:108066478:A:G	F857L	0.953
7:108103112:C:T	C371Y	0.953
7:108107763:C:A	W153C	0.951
7:108107763:C:G	W153C	0.951
7:108055880:G:C	F1169L	0.950
7:108055880:G:T	F1169L	0.950

dbSNP variants (sampled 300 via entrez): RS1000024306 (7:108049120 T>C), RS1000024748 (7:108027886 G>A,T), RS1000030559 (7:108099768 C>A), RS1000063762 (7:108113442 A>C), RS1000084442 (7:108058054 T>A,C), RS1000087279 (7:108100098 AT>A), RS1000174630 (7:108096533 G>T), RS1000191095 (7:108011223 T>A), RS1000193169 (7:108051161 T>C), RS1000219926 (7:108129631 A>G), RS1000227607 (7:108051417 A>G), RS1000243217 (7:108094188 C>T), RS1000271586 (7:108046166 C>G), RS1000281679 (7:108046506 C>A,G,T), RS1000301646 (7:108059274 T>A)

Disease associations

OMIM: gene MIM:616380 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001215_4	Coffee consumption	4.000000e-09
GCST003649_2	Pneumococcal bacteremia	8.000000e-06
GCST005956_26	Waist-to-hip ratio adjusted for BMI	2.000000e-08
GCST005962_48	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	2.000000e-06

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004330	coffee consumption
EFO:1001925	pneumococcal bacteremia
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement

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

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression	2
bisphenol A	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression	1
Air Pollutants	decreases expression	1
Lipopolysaccharides	affects cotreatment, increases expression	1
Mercury	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Asbestos, Crocidolite	increases methylation	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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