LAD1

Summary

LAD1 (ladinin 1, HGNC:6472) is a protein-coding gene on chromosome 1q32.1, encoding Ladinin-1 (O00515). Anchoring filament protein which is a component of the basement membrane zone.

The protein encoded by this gene may be an anchoring filament that is a component of basement membranes. It may contribute to the stability of the association of the epithelial layers with the underlying mesenchyme.

Source: NCBI Gene 3898 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 33 total
• MANE Select transcript: NM_005558

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6472
Approved symbol	LAD1
Name	ladinin 1
Location	1q32.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000159166
Ensembl biotype	protein_coding
OMIM	602314
Entrez	3898

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 13 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000367313, ENST00000391967, ENST00000475136, ENST00000488842, ENST00000631576, ENST00000632743, ENST00000633953, ENST00000909137, ENST00000909138, ENST00000909139, ENST00000909140, ENST00000909141, ENST00000909142, ENST00000909143, ENST00000942862

RefSeq mRNA: 1 — MANE Select: NM_005558 NM_005558

CCDS: CCDS1410

Canonical transcript exons

ENST00000391967 — 10 exons

Exon	Start	End
ENSE00000791360	201382653	201382739
ENSE00001043690	201384792	201384835
ENSE00001043718	201385701	201385805
ENSE00001137361	201383317	201383389
ENSE00001192652	201386335	201387178
ENSE00001192656	201389160	201389303
ENSE00001329048	201382252	201382326
ENSE00001444189	201380833	201381893
ENSE00001444190	201399269	201399324
ENSE00003466289	201383074	201383211

Expression profiles

Bgee: expression breadth ubiquitous, 198 present calls, max score 99.30.

FANTOM5 (CAGE): breadth broad, TPM avg 9.9858 / max 301.1142, expressed in 472 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
16639	4.2933	397
16641	3.1147	324
16642	1.5176	326
16640	0.7277	285
16644	0.2641	69
16643	0.0254	6
201869	0.0248	9
201870	0.0184	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	99.30	gold quality
skin of abdomen	UBERON:0001416	98.32	gold quality
esophagus mucosa	UBERON:0002469	98.25	gold quality
skin of leg	UBERON:0001511	97.85	gold quality
mucosa of transverse colon	UBERON:0004991	97.82	gold quality
endometrium epithelium	UBERON:0004811	97.03	gold quality
gall bladder	UBERON:0002110	96.51	gold quality
ileal mucosa	UBERON:0000331	96.39	gold quality
zone of skin	UBERON:0000014	96.35	gold quality
gingiva	UBERON:0001828	95.82	gold quality
gingival epithelium	UBERON:0001949	95.58	gold quality
tongue squamous epithelium	UBERON:0006919	95.16	gold quality
rectum	UBERON:0001052	95.03	gold quality
colonic epithelium	UBERON:0000397	94.96	gold quality
pharyngeal mucosa	UBERON:0000355	94.72	gold quality
body of pancreas	UBERON:0001150	94.27	gold quality
mammalian vulva	UBERON:0000997	93.35	gold quality
upper arm skin	UBERON:0004263	93.07	gold quality
oral cavity	UBERON:0000167	92.56	gold quality
pancreas	UBERON:0001264	91.73	gold quality
metanephros cortex	UBERON:0010533	91.72	gold quality
oocyte	CL:0000023	91.15	gold quality
epithelium of esophagus	UBERON:0001976	91.08	gold quality
upper leg skin	UBERON:0004262	90.50	gold quality
esophagus squamous epithelium	UBERON:0006920	90.36	gold quality
tonsil	UBERON:0002372	90.33	gold quality
islet of Langerhans	UBERON:0000006	89.96	gold quality
nipple	UBERON:0002030	89.04	gold quality
colonic mucosa	UBERON:0000317	88.63	gold quality
small intestine Peyer’s patch	UBERON:0003454	88.53	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-7381	yes	1079.71
E-HCAD-1	yes	234.14
E-MTAB-8410	yes	44.10
E-MTAB-5061	yes	28.20
E-GEOD-81547	yes	22.20
E-HCAD-10	yes	13.46
E-GEOD-83139	yes	11.92
E-MTAB-8498	yes	11.23
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): DNMT3B, NR3C1

miRNA regulators (miRDB)

54 targeting LAD1, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-7845-5P	99.88	64.88	771
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-8073	99.86	65.21	1118
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-378A-5P	99.65	66.33	1311
HSA-MIR-497-3P	99.61	69.71	1990
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-4318	99.38	66.94	1505
HSA-MIR-580-5P	99.28	70.94	1776
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-6803-5P	99.19	63.90	1026

Literature-anchored findings (GeneRIF, showing 8)

• Calcium regulation of EGF-induced ERK5 activation is mediated through interaction of MEKK2 with the adaptor protein Lad1. (PMID:20830310)
• Here, we focus on the trSNP in LAD1, a gene that encodes for Ladinin-1, a collagenous anchoring filament protein of basement membrane that is responsible for maintaining cohesion at the dermal-epidermal junction. (PMID:25605789)
• Basement membrane protein ladinin-1 and the MIF-CD44-beta1 integrin signaling axis are implicated in laryngeal cancer metastasis (PMID:27460703)
• High abundance of LAD1 is associated with breast cancer. (PMID:29382783)
• High expression of ladinin-1 (LAD1) predicts adverse outcomes: a new candidate docetaxel resistance gene for prostatic cancer (PCa). (PMID:34516317)
• Ladinin 1 Shortens Survival via Promoting Proliferation and Enhancing Invasiveness in Lung Adenocarcinoma. (PMID:36613882)
• The Tumorigenic Effect of the High Expression of Ladinin-1 in Lung Adenocarcinoma and Its Potential as a Therapeutic Target. (PMID:36770773)
• Ladinin-1 in actin arcs of oral squamous cell carcinoma is involved in cell migration and epithelial phenotype. (PMID:39354061)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Lad1	ENSMUSG00000041782
rattus_norvegicus	Lad1	ENSRNOG00000009144

Protein

Protein identifiers

Ladinin-1 — O00515 (reviewed: O00515)

Alternative names: Linear IgA disease antigen

All UniProt accessions (5): A0A0J9YVY2, A0A0J9YW63, A0A0J9YYF6, E9PDI4, O00515

UniProt curated annotations — full annotation on UniProt →

Function. Anchoring filament protein which is a component of the basement membrane zone.

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

RefSeq proteins (1): NP_005549* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR017404	Ladinin_1	Family

UniProt features (35 total): modified residue 10, repeat 8, compositionally biased region 7, sequence variant 6, region of interest 3, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00515-F1	53.77	0.04

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 (10): 38, 64, 78, 121, 123, 347, 356, 394, 424, 485

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 173 (showing top): RNGTGGGC_UNKNOWN, JAEGER_METASTASIS_DN, ENK_UV_RESPONSE_KERATINOCYTE_UP, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, RICKMAN_METASTASIS_DN, MARTINEZ_RB1_TARGETS_DN, CHARAFE_BREAST_CANCER_BASAL_VS_MESENCHYMAL_UP, LINDGREN_BLADDER_CANCER_CLUSTER_2A_UP, ABE_VEGFA_TARGETS_2HR, JIANG_TIP30_TARGETS_DN, BOYAULT_LIVER_CANCER_SUBCLASS_G1_UP, GRUETZMANN_PANCREATIC_CANCER_UP, GOCC_BASEMENT_MEMBRANE, VANTVEER_BREAST_CANCER_ESR1_DN, MODULE_38

GO Biological Process (0):

GO Molecular Function (2): structural molecule activity (GO:0005198), cadherin binding (GO:0045296)

GO Cellular Component (4): basement membrane (GO:0005604), actin cytoskeleton (GO:0015629), extracellular exosome (GO:0070062), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
molecular_function	1
cell adhesion molecule binding	1
extracellular matrix	1
cytoskeleton	1
extracellular vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

756 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LAD1	EPHA4	P54764	806
LAD1	LRFN5	Q96NI6	444
LAD1	DAZAP1	Q96EP5	421
LAD1	VTN	P01141	415
LAD1	FN1	P02751	414
LAD1	FREM3	P0C091	387
LAD1	LRIT1	Q9P2V4	381
LAD1	PROKR1	Q8TCW9	354
LAD1	PROKR2	Q8NFJ6	353
LAD1	HUS1	O60921	353
LAD1	IGFBP7	Q16270	353
LAD1	ST3GAL1	Q11201	353
LAD1	MTRR	Q9UBK8	353
LAD1	WDR24	Q96S15	348
LAD1	CDS2	O95674	335

IntAct

31 interactions, top by confidence:

A	B	Type	Score
	LAD1	psi-mi:“MI:0407”(direct interaction)	0.440
SFN	LAD1	psi-mi:“MI:0915”(physical association)	0.400
LAD1	E6	psi-mi:“MI:0915”(physical association)	0.370
SPHK1	MYO1C	psi-mi:“MI:0914”(association)	0.350
PLEKHA7	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
L1TD1	MYO1C	psi-mi:“MI:0914”(association)	0.350
PRKD1		psi-mi:“MI:0914”(association)	0.350
ESR2		psi-mi:“MI:0914”(association)	0.350
PIK3CA	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
rep	LAD1	psi-mi:“MI:0914”(association)	0.350
	PDLIM1	psi-mi:“MI:0914”(association)	0.350
TMIGD1	LAD1	psi-mi:“MI:0914”(association)	0.350
	GTPBP10	psi-mi:“MI:0914”(association)	0.350
GOT1	A2ML1	psi-mi:“MI:0914”(association)	0.350
PPP2R2B	A2ML1	psi-mi:“MI:0914”(association)	0.350
	SUPT5H	psi-mi:“MI:0914”(association)	0.350
AHI1	LAD1	psi-mi:“MI:0914”(association)	0.350
METAP2	LAD1	psi-mi:“MI:0914”(association)	0.350
RPL7A	LAD1	psi-mi:“MI:0914”(association)	0.350
TIPARP	LAD1	psi-mi:“MI:0914”(association)	0.350
LAD1	ZZEF1	psi-mi:“MI:0914”(association)	0.350
FEM1A	LAD1	psi-mi:“MI:0914”(association)	0.350
LAD1	FLNB	psi-mi:“MI:0914”(association)	0.350
SMPD2	A2ML1	psi-mi:“MI:0914”(association)	0.350
NS1	LRRD1	psi-mi:“MI:0914”(association)	0.350
MCM7		psi-mi:“MI:0914”(association)	0.350
CDH1	ESYT2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (72): LAD1 (Affinity Capture-MS), LAD1 (Proximity Label-MS), LAD1 (Affinity Capture-MS), LAD1 (Affinity Capture-MS), LAD1 (Affinity Capture-MS), LAD1 (Affinity Capture-MS), LAD1 (Affinity Capture-MS), LAD1 (Affinity Capture-MS), LAD1 (Affinity Capture-MS), HECTD3 (Affinity Capture-MS), LAD1 (Affinity Capture-MS), ACOX1 (Affinity Capture-MS), NCK1 (Affinity Capture-MS), FAM101B (Affinity Capture-MS), WDR26 (Affinity Capture-MS)

ESM2 similar proteins: A0A8I5ZM56, A2AG50, A2AI08, A2AJI0, A5D7K1, D4A4L4, E1C2Q8, F1LR10, O00515, O14529, O75128, O88573, O88735, P51825, P57016, Q14244, Q32LQ1, Q3KQU3, Q3U2K0, Q5JTD0, Q5NBX1, Q5PR69, Q5R7F9, Q5XHX2, Q5ZIA2, Q5ZJJ1, Q68DK7, Q6IPM2, Q6NV74, Q6NZF1, Q6PDH0, Q6PDM1, Q6PG95, Q6ZU35, Q86UU1, Q8CCJ4, Q8K124, Q8N7J2, Q8TD55, Q96PV7

Diamond homologs: O00515, P57016

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	8
Likely benign	1
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

3313 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:201389259:C:G	R28P	0.982
1:201382694:A:G	W478R	0.981
1:201382694:A:T	W478R	0.981
1:201399285:A:G	W8R	0.981
1:201399285:A:T	W8R	0.981
1:201399283:C:A	W8C	0.979
1:201399283:C:G	W8C	0.979
1:201382692:C:A	W478C	0.972
1:201382692:C:G	W478C	0.972
1:201383125:A:C	F445L	0.972
1:201383125:A:T	F445L	0.972
1:201383127:A:G	F445L	0.972
1:201389247:C:G	R32P	0.970
1:201383334:A:C	Y411D	0.968
1:201385704:A:C	F376L	0.965
1:201385704:A:T	F376L	0.965
1:201385706:A:G	F376L	0.965
1:201389253:C:G	R30P	0.961
1:201389249:C:A	R31S	0.959
1:201389249:C:G	R31S	0.959
1:201389260:G:T	R28S	0.959
1:201389301:A:G	L14P	0.957
1:201399293:C:A	R5M	0.954
1:201383325:C:G	A414P	0.951
1:201383126:A:C	F445C	0.947
1:201383136:G:T	R442S	0.945
1:201389278:C:G	D22H	0.944
1:201383135:C:G	R442P	0.943
1:201383137:C:A	K441N	0.939
1:201383137:C:G	K441N	0.939

dbSNP variants (sampled 300 via entrez): RS1000133133 (1:201400081 T>G), RS1000227609 (1:201393573 C>T), RS1000264306 (1:201387388 C>T), RS1000285350 (1:201386092 G>C), RS1000337205 (1:201385876 T>A,G), RS1000447684 (1:201380668 T>C), RS1000530684 (1:201391953 G>A,C), RS1000682848 (1:201396451 T>G), RS1000696662 (1:201387652 C>T), RS1000755039 (1:201381007 G>T), RS1001045116 (1:201397943 G>A), RS1001220254 (1:201388490 C>G), RS1001313377 (1:201388775 G>A,T), RS1001357764 (1:201393964 A>C), RS1001530636 (1:201398677 T>C)

Disease associations

OMIM: gene MIM:602314 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST006436_2	Triglyceride levels	2.000000e-17
GCST008163_18	Height	4.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, decreases expression, increases abundance, increases expression	4
Air Pollutants	increases expression, affects cotreatment, increases abundance, increases oxidation, decreases expression	4
Acetaminophen	decreases expression	3
Tobacco Smoke Pollution	affects expression, decreases expression, increases expression	3
Particulate Matter	decreases expression, increases abundance, increases expression, affects cotreatment	3
Decitabine	affects expression, decreases expression, decreases reaction	2
Arsenic	decreases expression, increases abundance, increases expression	2
Benzo(a)pyrene	decreases methylation, increases expression	2
Estradiol	increases expression	2
Smoke	increases abundance, increases expression, decreases expression, decreases reaction	2
Valproic Acid	decreases expression, increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
sotorasib	decreases expression, affects cotreatment	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
uranyl acetate	affects expression	1
propionaldehyde	decreases expression	1
bisphenol A	decreases methylation	1
deoxynivalenol	increases expression	1
pyrogallol 1,3-dimethyl ether	decreases expression, affects cotreatment, affects localization, increases expression	1
ethyl-p-hydroxybenzoate	increases expression	1
manganese chloride	decreases expression, increases abundance	1
nickel sulfate	increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
CGP 52608	affects binding, increases reaction	1
3-nitrobenzanthrone	increases expression	1
abrine	increases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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