LCN2

Summary

LCN2 (lipocalin 2, HGNC:6526) is a protein-coding gene on chromosome 9q34.11, encoding Neutrophil gelatinase-associated lipocalin (P80188). Iron-trafficking protein involved in multiple processes such as apoptosis, innate immunity and renal development.

This gene encodes a protein that belongs to the lipocalin family. Members of this family transport small hydrophobic molecules such as lipids, steroid hormones and retinoids. The protein encoded by this gene is a neutrophil gelatinase-associated lipocalin and plays a role in innate immunity by limiting bacterial growth as a result of sequestering iron-containing siderophores. The presence of this protein in blood and urine is an early biomarker of acute kidney injury. This protein is thought to be be involved in multiple cellular processes, including maintenance of skin homeostasis, and suppression of invasiveness and metastasis. Mice lacking this gene are more susceptible to bacterial infection than wild type mice.

Source: NCBI Gene 3934 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 50 total — 1 pathogenic
• MANE Select transcript: NM_005564

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6526
Approved symbol	LCN2
Name	lipocalin 2
Location	9q34.11
Locus type	gene with protein product
Status	Approved
Aliases	NGAL, 24p3
Ensembl gene	ENSG00000148346
Ensembl biotype	protein_coding
OMIM	600181
Entrez	3934

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 protein_coding, 2 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000277480, ENST00000372998, ENST00000373017, ENST00000470902, ENST00000487719, ENST00000488391, ENST00000494317, ENST00000886526, ENST00000886527

RefSeq mRNA: 1 — MANE Select: NM_005564 NM_005564

CCDS: CCDS6892

Canonical transcript exons

ENST00000277480 — 7 exons

Exon	Start	End
ENSE00000984625	128150238	128150374
ENSE00001146095	128149453	128149663
ENSE00001909922	128153311	128153453
ENSE00003540781	128151638	128151717
ENSE00003568753	128153100	128153126
ENSE00003651301	128151906	128152025
ENSE00003665140	128152183	128152284

Expression profiles

Bgee: expression breadth ubiquitous, 221 present calls, max score 99.98.

FANTOM5 (CAGE): breadth broad, TPM avg 128.3846 / max 61947.4301, expressed in 499 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
98706	126.9289	493
98707	0.8907	153
98708	0.2692	60
98718	0.0994	28
98721	0.0703	20
98720	0.0522	14
98719	0.0518	14
98717	0.0120	5
98722	0.0102	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
palpebral conjunctiva	UBERON:0001812	99.98	gold quality
nasal cavity epithelium	UBERON:0005384	99.91	gold quality
nasal cavity mucosa	UBERON:0001826	99.74	gold quality
epithelium of bronchus	UBERON:0002031	99.72	gold quality
bronchial epithelial cell	CL:0002328	99.70	gold quality
trabecular bone tissue	UBERON:0002483	99.70	gold quality
bronchus	UBERON:0002185	99.68	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.68	gold quality
type B pancreatic cell	CL:0000169	99.67	gold quality
bone marrow	UBERON:0002371	99.64	gold quality
gall bladder	UBERON:0002110	99.56	gold quality
bone marrow cell	CL:0002092	99.51	gold quality
oral cavity	UBERON:0000167	99.13	gold quality
pharyngeal mucosa	UBERON:0000355	99.08	gold quality
trachea	UBERON:0003126	98.87	gold quality
mucosa of stomach	UBERON:0001199	98.61	gold quality
esophagus mucosa	UBERON:0002469	98.59	gold quality
urethra	UBERON:0000057	98.58	gold quality
minor salivary gland	UBERON:0001830	98.58	gold quality
islet of Langerhans	UBERON:0000006	98.34	gold quality
saliva-secreting gland	UBERON:0001044	98.23	gold quality
epithelium of nasopharynx	UBERON:0001951	97.74	gold quality
mouth mucosa	UBERON:0003729	97.70	gold quality
lower esophagus mucosa	UBERON:0035834	97.58	gold quality
body of tongue	UBERON:0011876	97.28	gold quality
rectum	UBERON:0001052	97.23	gold quality
buccal mucosa cell	CL:0002336	96.99	gold quality
parotid gland	UBERON:0001831	96.78	gold quality
epithelial cell of pancreas	CL:0000083	96.77	gold quality
pancreatic ductal cell	CL:0002079	96.58	silver quality

Single-cell (SCXA)

Detected in 21 experiment(s), a significant marker in 20.

Experiment	Marker?	Max mean expression
E-CURD-114	yes	22017.66
E-MTAB-6701	yes	13244.20
E-CURD-11	yes	9488.42
E-HCAD-15	yes	8885.64
E-MTAB-5061	yes	6498.86
E-MTAB-10662	yes	3153.13
E-MTAB-10283	yes	2215.73
E-GEOD-86618	yes	1916.57
E-GEOD-125970	yes	1246.10
E-MTAB-10596	yes	1167.71
E-MTAB-8559	yes	953.56
E-MTAB-8410	yes	56.65
E-GEOD-81547	yes	21.57
E-HCAD-1	yes	20.24
E-GEOD-83139	yes	13.43

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
SLC22A17	Unknown

Upstream regulators (CollecTRI, top): CEBPB, CEBPD, CEBPE, DDIT3, ESR1, GATA1, IRF6, NFATC4, NFIA, NFKB1, NFKB, NFKBIZ, NR3C1, NR3C2, RELA, SPI1, STAT1, STAT3, STAT5A, STAT5B

miRNA regulators (miRDB)

5 targeting LCN2, 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-4283	100.00	66.42	2097
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-374B-3P	98.63	68.24	1360
HSA-MIR-4469	97.93	65.81	1319
HSA-MIR-3616-3P	96.96	65.45	983

Literature-anchored findings (GeneRIF, showing 40)

• up-regulated by the AML1-MTG8 fusion protein, suggesting a role in the granulocytic maturation characteristic of the t(8;21) acute myelogenous leukemia (PMID:11986950)
• the transient interfollicular NGAL expression during skin embryogenesis along with the induction of NGAL in adult parakeratotic epidermis suggests it play a role in epithelial differentiation pathways (PMID:12473066)
• is endocytosed by megalin, and this endocytosis is blocked by an antibody against megalin (PMID:15670845)
• These data characterize lipocalin 2 as an epithelial inducer in Ras malignancy and a suppressor of metastasis. (PMID:15691834)
• Data show that Ngal protects the kidney and mitigates azotemia during ischemia-reperfusion injury. (PMID:15711640)
• The role of NGAL on chemically-induced apoptosis in tumor cell lines is reported. (PMID:16060857)
• NGAL may play an important role in breast cancer in vivo by protecting MMP-9 from degradation, thereby enhancing its enzymatic activity and facilitating angiogenesis and tumor growth (PMID:16061852)
• major differences exist between mouse and man with regards to the role of NGAL in myelopoiesis and inflammation (PMID:16146540)
• NGAL/24p3 is increased in atherosclerotic plaques and myocardial infarction (PMID:16254208)
• LCN2 may have multifunctional roles in the maintenance of skin homeostasis. (PMID:16374475)
• NGAL may be a candidate metastasis suppressor in colon cancer cells (PMID:16381001)
• 4-HPR markedly induces LCN2 expression, but this event may not represent an apoptotic response (PMID:16671099)
• The analysis of PLAT and LCN2 transcripts in 12 samples obtained through EUS-guided FNA from patients with pancreatic adenocarcinoma showed significantly increased expression levels in comparison with those found in normal tissues. (PMID:16733850)
• a detailed analysis of the 24p3 promoter;24p3 is regulated primarily at the level of transcription rather than mRNA stability (PMID:16798734)
• urine NGAL and interleukin 18 represent early, predictive biomarkers of delayed graft function (PMID:16827865)
• Lipocalin 2 can suppress the ras-induced expression of vascular endothelial growth factor in 4T1 cells via down-regulation of ras mitogen-activated protein kinase and ras phosphatidylinositol-3-kinase signaling. (PMID:17114340)
• dual effects of NGAL as a siderophore:iron-binding protein and as a growth factor and examines the role of these effects in renal injury [REVIEW] (PMID:17229907)
• NGAL (neutrophil gelatinase-associated lipocalin) receptor-3 may act as a potential NGAL receptor and play a role in NGAL-mediated iron transport in oesophageal carcinoma[neutrophil gelatinase-associated lipocalin receptor] (PMID:17253959)
• NGAL may be a good marker to monitor changes of benign to premalignant and malignant ovarian tumors and that the molecule may be involved in the progression of epithelial ovarian malignancies (PMID:17294443)
• Findings suggest the promising use of urinary NGAL as an early biomarker for tubulointerstitial injury of IgA nephropathy and perhaps other types of renal disease in general. (PMID:17360238)
• Urinary lipocalin-2 is a potential marker of the presence and severity of renal involvement in adult patients with systemic lupus erythematosus. (PMID:17530720)
• NGAL expression is a predictor of poor prognosis in primary human breast cancer (PMID:17554627)
• Autosomal-dominant polycystic kidney disease patients with higher cystic growth presented higher sNGAL and uNGAL levels. (PMID:17570904)
• NGAL in complex with activated MMP-9 is present in AAA wall and thrombus. (PMID:17721627)
• NGAL mRNA transcripts were detected in salivary gland tissue with chronic sialadenitis; only a small amount was detected in tissues from normal salivary glands; results imply that NGAL is associated with regulation of inflammation in salivary glands (PMID:17847728)
• NGAL is an early predictive biomarker of contrast-induced nephropathy in children. (PMID:17874137)
• NGAL may represent a sensitive early biomarker of renal impairment after percutaneous coronary interventions. (PMID:17901710)
• NGAL protects MMP-9 activity and is relevant to cartilage matrix degradation in OA,may represent mechanism by which NGAL contributes to the loss of cartilage matrix proteins in osteoarthritis. (PMID:17907186)
• Results show that neutrophil gelatinase-associated lipocalin (NGAL or lipocalin-2)is co-expressed with migration stimulating factor (MSF) by keratinocytes and acts as a functional inhibitor of MSF. (PMID:17949711)
• Review validates the role of neutrophil gelatinase-associated lipocalin (NGAL) as an early biomarker of acute kidney injury (AKI) that rises significantly in AKI patients before the rise in creatinine is seen. (PMID:18001501)
• Lineage-specific role for LCN2 in human hematopoiesis that is reminiscent of its effects upon mouse hematopoiesis. Important in vivo function of LCN2 in the regulation of human hematopoiesis. (PMID:18064607)
• Plasma NGAL is an early predictive biological marker of acute kidney disease, morbidity and mortality following pediatric cardiac surgery. (PMID:18070344)
• Hypertension is associated with kidney injury as reflected by elevated serum NGAL and cystatin C. (PMID:18275504)
• We conclude that urinary IL-18 or NGAL could be early biomarkers of CIN and that urinary IL-18 is well associated with the later cardiac outcomes in patients after coronary angiography. (PMID:18287807)
• selectively induce Neutrophil gelatinase expression in sebaceous glands might represent therapeutic alternatives to the use of 13-cis retinoic acid to treat individuals with acne (PMID:18317594)
• Urine NGAL is an early predictive biomarker of acute kidney injury severity after cardiopulmonary bypass. (PMID:18337554)
• NGAL and MMP-9/NGAL complex suppression might have a protective role in women with PCOS. (PMID:18362300)
• adult beta-thalassemia patients upregulated NGAL expression compared to normal samples; no upregulation was observed in pediatric patients; upregulation may play an important role in decreasing reactive oxygen species or iron in beta-thalassemia patients (PMID:18375251)
• NGAL is highly expressed in early dysplastic lesions in the pancreas, suggesting a possible role as an early diagnostic marker for pancreatic cancer. (PMID:18392050)
• The association between serum lipocalin-2 and obesity or metabolic syndrome was not validated in this study. (PMID:18393169)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Lcn2	ENSMUSG00000026822
rattus_norvegicus	Lcn2	ENSRNOG00000013973

Paralogs (12): PTGDS (ENSG00000107317), PAEP (ENSG00000122133), OBP2A (ENSG00000122136), LCN9 (ENSG00000148386), LCN1 (ENSG00000160349), OBP2B (ENSG00000171102), LCN15 (ENSG00000177984), LCN12 (ENSG00000184925), LCN10 (ENSG00000187922), LCN8 (ENSG00000204001), LCNL1 (ENSG00000214402), LCN6 (ENSG00000267206)

Protein

Protein identifiers

Neutrophil gelatinase-associated lipocalin — P80188 (reviewed: P80188)

Alternative names: 25 kDa alpha-2-microglobulin-related subunit of MMP-9, Lipocalin-2, Oncogene 24p3, Siderocalin, p25

All UniProt accessions (2): P80188, X6R8F3

UniProt curated annotations — full annotation on UniProt →

Function. Iron-trafficking protein involved in multiple processes such as apoptosis, innate immunity and renal development. Binds iron through association with 2,3-dihydroxybenzoic acid (2,3-DHBA), a siderophore that shares structural similarities with bacterial enterobactin, and delivers or removes iron from the cell, depending on the context. Iron-bound form (holo-24p3) is internalized following binding to the SLC22A17 (24p3R) receptor, leading to release of iron and subsequent increase of intracellular iron concentration. In contrast, association of the iron-free form (apo-24p3) with the SLC22A17 (24p3R) receptor is followed by association with an intracellular siderophore, iron chelation and iron transfer to the extracellular medium, thereby reducing intracellular iron concentration. Involved in apoptosis due to interleukin-3 (IL3) deprivation: iron-loaded form increases intracellular iron concentration without promoting apoptosis, while iron-free form decreases intracellular iron levels, inducing expression of the proapoptotic protein BCL2L11/BIM, resulting in apoptosis. Involved in innate immunity; limits bacterial proliferation by sequestering iron bound to microbial siderophores, such as enterobactin. Can also bind siderophores from M.tuberculosis.

Subunit / interactions. Monomer. Homodimer; disulfide-linked. Heterodimer; disulfide-linked with MMP9.

Subcellular location. Secreted. Cytoplasmic granule lumen. Cytoplasmic vesicle lumen.

Tissue specificity. Detected in neutrophils (at protein level). Expressed in bone marrow and in tissues that are prone to exposure to microorganism. High expression is found in bone marrow as well as in uterus, prostate, salivary gland, stomach, appendix, colon, trachea and lung. Expressed in the medullary tubules of the kidney. Not found in the small intestine or peripheral blood leukocytes.

Induction. Expression is activated by the oncoprotein BCR-ABL; BCR-ABL misregulates expression via the JAK/STAT pathway and binding of STAT5A to the promoter. Induced by insulin.

Similarity. Belongs to the calycin superfamily. Lipocalin family.

Isoforms (2)

UniProt ID	Names	Canonical?
P80188-1	1	yes
P80188-2	2

RefSeq proteins (1): NP_005555* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000566	Lipocln_cytosolic_FA-bd_dom	Domain
IPR002345	Lipocalin	Family
IPR003087	LCN2/LCN12	Family
IPR012674	Calycin	Homologous_superfamily
IPR022272	Lipocalin_CS	Conserved_site

Pfam: PF00061

UniProt features (36 total): strand 10, helix 6, binding site 6, sequence conflict 5, mutagenesis site 2, signal peptide 1, chain 1, disulfide bond 1, splice variant 1, turn 1, modified residue 1, glycosylation site 1

Structure

Experimental structures (PDB)

59 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
6GQZ	X-RAY DIFFRACTION	1.4
4MVK	X-RAY DIFFRACTION	1.5
5N48	X-RAY DIFFRACTION	1.6
4MVI	X-RAY DIFFRACTION	1.7
6Z6Z	X-RAY DIFFRACTION	1.78
6S8V	X-RAY DIFFRACTION	1.8
6Z2C	X-RAY DIFFRACTION	1.8
4IAX	X-RAY DIFFRACTION	1.9
6QMU	X-RAY DIFFRACTION	1.98
3DSZ	X-RAY DIFFRACTION	2
5MHH	X-RAY DIFFRACTION	2
8UYN	X-RAY DIFFRACTION	2
4ZHC	X-RAY DIFFRACTION	2.04
4ZHH	X-RAY DIFFRACTION	2.04
4ZHD	X-RAY DIFFRACTION	2.05
4ZHG	X-RAY DIFFRACTION	2.05
8UZ9	X-RAY DIFFRACTION	2.08
1X71	X-RAY DIFFRACTION	2.1
1X89	X-RAY DIFFRACTION	2.1
4QAE	X-RAY DIFFRACTION	2.1
5KID	X-RAY DIFFRACTION	2.15
3CBC	X-RAY DIFFRACTION	2.17
3HWG	X-RAY DIFFRACTION	2.19
3PEC	X-RAY DIFFRACTION	2.19
1X8U	X-RAY DIFFRACTION	2.2
5NKN	X-RAY DIFFRACTION	2.2
3FW4	X-RAY DIFFRACTION	2.3
3FW5	X-RAY DIFFRACTION	2.3
3PED	X-RAY DIFFRACTION	2.3
3T1D	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P80188-F1	91.89	0.87

Functional residue map

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

Ligand- & substrate-binding residues (6): 72–74; 126; 145; 154; 154; 158

Post-translational modifications (1): 21

Disulfide bonds (1): 96–195

Glycosylation sites (1): 85

Mutagenesis-validated functional residues (2):

Position	Phenotype
145	strongly reduced affinity for catecholate-type ferric siderophores; when associated with a-154.
154	strongly reduced affinity for catecholate-type ferric siderophores; when associated with a-145.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling
R-HSA-6798695	Neutrophil degranulation
R-HSA-6799990	Metal sequestration by antimicrobial proteins
R-HSA-917937	Iron uptake and transport

MSigDB gene sets: 424 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_MEMORY, VERHAAK_AML_WITH_NPM1_MUTATED_DN, BROWNE_HCMV_INFECTION_4HR_UP, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_RESPONSE_TO_IONIZING_RADIATION, GOBP_EPITHELIUM_DEVELOPMENT, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_COGNITION, GOBP_BEHAVIOR, SWEET_KRAS_ONCOGENIC_SIGNATURE, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_ACID_CHEMICAL

GO Biological Process (47): acute-phase response (GO:0006953), short-term memory (GO:0007614), long-term memory (GO:0007616), response to xenobiotic stimulus (GO:0009410), response to virus (GO:0009615), response to herbicide (GO:0009635), response to blue light (GO:0009637), response to fructose (GO:0009750), response to iron(II) ion (GO:0010040), response to mycotoxin (GO:0010046), positive regulation of endothelial cell migration (GO:0010595), positive regulation of gene expression (GO:0010628), siderophore transport (GO:0015891), positive regulation of cell projection organization (GO:0031346), cellular response to nutrient levels (GO:0031669), cellular response to increased oxygen levels (GO:0036295), defense response to bacterium (GO:0042742), innate immune response (GO:0045087), cellular response to hydrogen peroxide (GO:0070301), cellular response to lipopolysaccharide (GO:0071222), cellular response to interleukin-1 (GO:0071347), cellular response to interleukin-6 (GO:0071354), cellular response to tumor necrosis factor (GO:0071356), cellular response to hypoxia (GO:0071456), cellular response to X-ray (GO:0071481), extrinsic apoptotic signaling pathway in absence of ligand (GO:0097192), positive regulation of hippocampal neuron apoptotic process (GO:0110090), negative regulation of hippocampal neuron apoptotic process (GO:0110091), positive regulation of cold-induced thermogenesis (GO:0120162), positive regulation of reactive oxygen species biosynthetic process (GO:1903428), response to kainic acid (GO:1904373), positive regulation of iron ion import across plasma membrane (GO:1904440), cellular response to amyloid-beta (GO:1904646), positive regulation of endothelial tube morphogenesis (GO:1905956), cellular response to nerve growth factor stimulus (GO:1990090), immune system process (GO:0002376), monoatomic ion transport (GO:0006811), iron ion transport (GO:0006826), apoptotic process (GO:0006915), response to oxidative stress (GO:0006979)

GO Molecular Function (7): protease binding (GO:0002020), iron ion binding (GO:0005506), identical protein binding (GO:0042802), iron ion sequestering activity (GO:0140315), enterobactin binding (GO:1903981), protein binding (GO:0005515), small molecule binding (GO:0036094)

GO Cellular Component (6): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), specific granule lumen (GO:0035580), extracellular exosome (GO:0070062), cytoplasmic vesicle (GO:0031410), cytoplasmic vesicle lumen (GO:0060205)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Signaling by Interleukins	1
Innate Immune System	1
Antimicrobial peptides	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
memory	2
response to toxic substance	2
binding	2
acute inflammatory response	1
response to chemical	1
response to other organism	1
response to stress	1
response to light stimulus	1
response to hexose	1
response to iron ion	1
regulation of endothelial cell migration	1
positive regulation of cell migration	1
endothelial cell migration	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
iron coordination entity transport	1
cell projection organization	1
regulation of cell projection organization	1
positive regulation of cellular component organization	1
response to nutrient levels	1
cellular response to stimulus	1
response to increased oxygen levels	1
cellular response to oxygen levels	1
defense response	1
response to bacterium	1
immune response	1
defense response to symbiont	1
cellular response to reactive oxygen species	1
response to hydrogen peroxide	1
response to lipopolysaccharide	1
cellular response to molecule of bacterial origin	1
cellular response to lipid	1
cellular response to oxygen-containing compound	1
enzyme binding	1
transition metal ion binding	1
protein binding	1
iron ion binding	1
metal ion sequestering activity	1
macrolide binding	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

286 interactions, top by confidence:

A	B	Type	Score
CCNC	LCN2	psi-mi:“MI:0915”(physical association)	0.670
GID8	PGRMC2	psi-mi:“MI:0914”(association)	0.640
LCN2	LCN2	psi-mi:“MI:0915”(physical association)	0.600
VEGFA	LCN2	psi-mi:“MI:0915”(physical association)	0.560
LCE3A	LCN2	psi-mi:“MI:0915”(physical association)	0.560
LCN2	LCE3A	psi-mi:“MI:0915”(physical association)	0.560
SGTA	LCN2	psi-mi:“MI:0915”(physical association)	0.560
ZBED1	LCN2	psi-mi:“MI:0915”(physical association)	0.560
LCN2	UBQLN1	psi-mi:“MI:0915”(physical association)	0.560
LCN2	TRIM32	psi-mi:“MI:0915”(physical association)	0.560
LCN2	UBQLN2	psi-mi:“MI:0915”(physical association)	0.560
RAMP2	LCN2	psi-mi:“MI:0915”(physical association)	0.560
LCN2	SGTB	psi-mi:“MI:0915”(physical association)	0.560
TRIAP1	LCN2	psi-mi:“MI:0915”(physical association)	0.560
LCN2	HDDC2	psi-mi:“MI:0915”(physical association)	0.560
LCN2	MAGED4B	psi-mi:“MI:0915”(physical association)	0.560
LCN2	PICK1	psi-mi:“MI:0915”(physical association)	0.560
LCN2	SCNM1	psi-mi:“MI:0915”(physical association)	0.560
LCN2	ODAPH	psi-mi:“MI:0915”(physical association)	0.560
CAMLG	LCN2	psi-mi:“MI:0915”(physical association)	0.560
LCN2	VEZF1	psi-mi:“MI:0915”(physical association)	0.560
CTDSP2	LCN2	psi-mi:“MI:0915”(physical association)	0.560
LCN2	BEX2	psi-mi:“MI:0915”(physical association)	0.560
LCN2	MSRB3	psi-mi:“MI:0915”(physical association)	0.560
P4HB	LCN2	psi-mi:“MI:0915”(physical association)	0.560
UBASH3A	LCN2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (177): LCN2 (Affinity Capture-MS), LCN2 (Affinity Capture-MS), LCN2 (Affinity Capture-MS), LCN2 (Affinity Capture-MS), LCN2 (Affinity Capture-MS), LCN2 (Affinity Capture-MS), LCN2 (Affinity Capture-MS), LCN2 (Affinity Capture-MS), LCN2 (Affinity Capture-MS), LCN2 (Affinity Capture-MS), LCN2 (Affinity Capture-MS), LCN2 (Affinity Capture-MS), LCN2 (Affinity Capture-MS), LCN2 (Affinity Capture-MS), LCN2 (Affinity Capture-MS)

ESM2 similar proteins: B3EY83, B5X0G2, H2B3G5, O02853, O09114, O18873, O97921, P02758, P02761, P04119, P07380, P09466, P11588, P11672, P13613, P19647, P20289, P22057, P30152, P31025, P33685, P33686, P33687, P33688, P41222, P41244, P53715, P62502, P62503, P80188, Q28388, Q29095, Q29487, Q29562, Q5VSP4, Q6JVE6, Q6JVL5, Q6UWW0, Q810Z1, Q8K1H9

Diamond homologs: B3EY83, P11672, P30152, P80188, Q6JVE5, Q6JVL5, O02853, O09114, O97921, P22057, P41222, Q01584, Q29095, Q29487, Q29562, Q6UWW0, Q8WNM0, Q8WNM1, Q9TUI1, Q9XS65, Q9XSM0, P02758, P21760, Q9I9P7, P00978, Q07456, Q60559, Q64240, A0A6P8HC43, A5X2X1, A6MFL3, A6MGY1, A8Y7N4, A8Y7N8, B2BS84, B5G6G6, B5KF95, B5KF96, B5KL36, B5L5M7

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
NfKb-p65/p50	“up-regulates quantity by expression”	LCN2	“transcriptional regulation”
NFAT5	“up-regulates quantity by expression”	LCN2	“transcriptional regulation”
hsa-miR-138-5p	“down-regulates quantity by destabilization”	LCN2	“post transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	25
Likely benign	4
Benign	4

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
831938	NC_000009.12:g.(?127815672)(128541180_?)del	Pathogenic

SpliceAI

1032 predictions. Top by Δscore:

Variant	Effect	Δscore
9:128151636:A:G	acceptor_gain	1.0000
9:128151716:GA:G	donor_gain	1.0000
9:128151718:G:GG	donor_gain	1.0000
9:128151896:AC:A	acceptor_gain	1.0000
9:128151897:C:CA	acceptor_gain	1.0000
9:128151897:C:G	acceptor_gain	1.0000
9:128151901:T:A	acceptor_gain	1.0000
9:128151901:TGCA:T	acceptor_loss	1.0000
9:128151902:GCAG:G	acceptor_loss	1.0000
9:128151904:A:AC	acceptor_loss	1.0000
9:128151904:A:AG	acceptor_gain	1.0000
9:128151904:AG:A	acceptor_gain	1.0000
9:128151905:G:GG	acceptor_gain	1.0000
9:128151905:GG:G	acceptor_gain	1.0000
9:128151905:GGT:G	acceptor_gain	1.0000
9:128151905:GGTT:G	acceptor_gain	1.0000
9:128151999:GGGA:G	donor_gain	1.0000
9:128152000:G:GT	donor_gain	1.0000
9:128152000:G:T	donor_gain	1.0000
9:128152023:ACGGT:A	donor_loss	1.0000
9:128152024:CGGTG:C	donor_loss	1.0000
9:128152025:GGT:G	donor_loss	1.0000
9:128152026:G:GA	donor_loss	1.0000
9:128152027:T:A	donor_loss	1.0000
9:128149243:G:GT	donor_gain	0.9900
9:128149664:G:GG	donor_gain	0.9900
9:128151634:CAAGG:C	acceptor_loss	0.9900
9:128151635:AAG:A	acceptor_gain	0.9900
9:128151635:AAGG:A	acceptor_loss	0.9900
9:128151637:G:GG	acceptor_gain	0.9900

AlphaMissense

1297 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:128150250:T:A	W51R	0.997
9:128150250:T:C	W51R	0.997
9:128150252:G:C	W51C	0.997
9:128150252:G:T	W51C	0.997
9:128151696:T:C	F112L	0.992
9:128151698:C:A	F112L	0.992
9:128151698:C:G	F112L	0.992
9:128151965:G:C	A139P	0.989
9:128150239:T:C	F47S	0.988
9:128150239:T:G	F47C	0.988
9:128150238:T:C	F47L	0.987
9:128150240:C:A	F47L	0.987
9:128150240:C:G	F47L	0.987
9:128150251:G:C	W51S	0.987
9:128150361:T:C	S88P	0.987
9:128151966:C:A	A139D	0.986
9:128152187:A:C	R160S	0.986
9:128152187:A:T	R160S	0.986
9:128150244:G:T	G49W	0.984
9:128152020:T:C	L157P	0.984
9:128149649:T:C	F42L	0.983
9:128149651:C:A	F42L	0.983
9:128149651:C:G	F42L	0.983
9:128150263:G:A	G55D	0.983
9:128149650:T:G	F42C	0.982
9:128150349:T:G	Y84D	0.982
9:128151936:G:C	R129P	0.982
9:128151648:T:A	C96S	0.981
9:128151649:G:C	C96S	0.981
9:128150245:G:T	G49V	0.980

dbSNP variants (sampled 300 via entrez): RS1000597275 (9:128149840 C>A,G), RS1000705447 (9:128149277 G>A), RS1000781104 (9:128148009 G>T), RS1001390633 (9:128153281 C>G), RS1001627576 (9:128148358 G>T), RS1002219596 (9:128148925 C>A), RS1002422983 (9:128151929 C>T), RS1002593622 (9:128149220 A>C), RS1002599293 (9:128147617 T>G), RS1004218358 (9:128151377 G>A), RS1004315946 (9:128149847 A>C), RS1004527624 (9:128152743 G>C), RS1004597773 (9:128151564 C>T), RS1005402617 (9:128148969 G>A), RS1005433641 (9:128148728 C>G)

Disease associations

OMIM: gene MIM:600181 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

Binding affinities (BindingDB)

4 measured of 4 human assays (4 total across all organisms); most potent 4 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
Fluvibactin A	KD	12 nM
Vibriobactin A	KD	18 nM
Fluvibactin	KD	34 nM
Vibriobactin	KD	56 nM

PubChem BioAssay actives

4 with measured affinity, of 4 total; 4 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-[3-[[(2S,3R)-2-[(2,3-dihydroxybenzoyl)amino]-3-hydroxybutanoyl]-[3-[(2,3-dihydroxybenzoyl)amino]propyl]amino]propyl]-2,3-dihydroxybenzamide	1800100: Fluorescence quenching titrations from Article 10.1021/cb4002552: “Siderocalin outwits the coordination chemistry of vibriobactin, a siderophore of Vibrio cholerae.”	kd	0.0120	uM
N-[3-[[(2S,3R)-2-[(2,3-dihydroxybenzoyl)amino]-3-hydroxybutanoyl]-[3-[[(2S,3R)-2-[(2,3-dihydroxybenzoyl)amino]-3-hydroxybutanoyl]amino]propyl]amino]propyl]-2,3-dihydroxybenzamide	1800100: Fluorescence quenching titrations from Article 10.1021/cb4002552: “Siderocalin outwits the coordination chemistry of vibriobactin, a siderophore of Vibrio cholerae.”	kd	0.0180	uM
(4S,5R)-N,N-bis[3-[(2,3-dihydroxybenzoyl)amino]propyl]-2-(2,3-dihydroxyphenyl)-5-methyl-4,5-dihydro-1,3-oxazole-4-carboxamide	1800100: Fluorescence quenching titrations from Article 10.1021/cb4002552: “Siderocalin outwits the coordination chemistry of vibriobactin, a siderophore of Vibrio cholerae.”	kd	0.0340	uM
(4S,5R)-N-[3-[(2,3-dihydroxybenzoyl)amino]propyl]-2-(2,3-dihydroxyphenyl)-N-[5-[(5R)-2-(2,3-dihydroxyphenyl)-5-methyl-4,5-dihydro-1,3-oxazol-4-yl]-5-oxopentyl]-5-methyl-4,5-dihydro-1,3-oxazole-4-carboxamide	1800100: Fluorescence quenching titrations from Article 10.1021/cb4002552: “Siderocalin outwits the coordination chemistry of vibriobactin, a siderophore of Vibrio cholerae.”	kd	0.0560	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	decreases expression, increases expression, affects expression	7
sodium arsenite	affects binding, increases reaction, decreases methylation, decreases reaction, increases expression (+2 more)	5
Estradiol	increases reaction, affects cotreatment, decreases expression, increases expression, affects binding	4
Tretinoin	increases expression, increases secretion	4
Cadmium Chloride	decreases secretion, increases abundance, increases expression	4
Particulate Matter	increases abundance, increases expression, decreases expression	4
Air Pollutants	increases abundance, increases expression, decreases expression	3
Benzo(a)pyrene	decreases methylation, increases expression, affects methylation, decreases expression	3
Cisplatin	affects cotreatment, increases expression, decreases secretion, decreases reaction	3
Tunicamycin	affects response to substance, increases expression	3
Cyclosporine	increases expression	3
bisphenol A	increases expression, decreases expression	2
Acetaminophen	affects cotreatment, increases expression, decreases expression, decreases secretion	2
Cadmium	increases abundance, increases expression	2
Nickel	increases expression	2
Silicon Dioxide	decreases expression	2
Smoke	decreases expression, increases abundance	2
Valproic Acid	affects reaction, increases expression, increases methylation	2
Isotretinoin	increases expression	2
3,19-(2-bromobenzylidene)andrographolide	decreases response to substance, increases expression	1
4-oxoretinoic acid	increases expression	1
propionaldehyde	increases expression	1
glycidyl methacrylate	decreases expression	1
potassium perchlorate	decreases expression	1
potassium persulfate	increases expression	1
di-n-octyl phthalate	increases abundance, increases secretion	1
3,4-dichloroaniline	increases expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cobaltous chloride	decreases expression	1

Cellosaurus cell lines

3 cell lines: 2 spontaneously immortalized cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B0YV	Abcam SW480 LCN2 KO	Cancer cell line	Male
CVCL_C1J5	CHO NGAL rAg 662	Spontaneously immortalized cell line	Female
CVCL_C1J6	CHO NGAL rAg C87S	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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