LCN2

protein-coding

lipocalin 2, the group of Lipocalins

Gene summary

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. [provided by RefSeq, Sep 2015]

MANE transcript

NM_005564.5

Inheritance

—

ClinVar variants

U:32B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.11

Max pathogenic AF

—

Genomic locus

chr9:128,149,071-128,153,453

External References & Databases

Ensembl (ENSG00000148346)

Transcript & Mutation Effects

hg38 • Region Span ~4.4 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to LCN2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 26

not providedTotal: 7

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005564.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar		1
missense			25 clinvar	2 clinvar	1 clinvar	28
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	32	3	1	36

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 13 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005564.5	RefSeq	NP_005555.2	6	MANE Select
ENST00000277480.7	Ensembl	ENSP00000277480.2	6	MANE Select
ENST00000372998.1	Ensembl	ENSP00000362089.1	7	Standard
ENST00000372998.2	Ensembl	ENSP00000362089.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

IL-17 signaling pathway - Homo sapiens (human)
Interleukin-4 and 13 signaling
Neutrophil degranulation
Antimicrobial peptides
Innate Immune System

Biological Process

cellular iron ion homeostasis
response to virus
response to herbicide
response to mycotoxin
positive regulation of gene expression

Molecular Function

protease binding
iron ion binding
small molecule binding
protein homodimerization activity
enterobactin binding

Cellular Component

extracellular region
extracellular space
cytosol
specific granule lumen
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000373017
Coding exons: 6
Length: 4385
Individuals with no LoFs: 125653
Homozygous LoFs: 0
Heterozygous LoFs: 94
Defined: 125747
p: 0.000374

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.431	122	109	1.12	0.00000592	1292
Missense (PolyPhen)		28	25.769	1.0866		332
Synonymous	0.957	41	49.6	0.827	0.00000303	384
Loss of Function	-0.350	13	11.7	1.11	5.84e-7	128

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0031	0.0031	notable
Latino/Admixed American	0.00081	0.00081	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.000079	0.000062	rare
South Asian	0.000065	0.000065	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Iron-trafficking protein involved in multiple processes such as apoptosis, innate immunity and renal development. Binds iron through association with 2,5-dihydroxybenzoic acid (2,5- 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, possibly by sequestrating iron, leading to limit bacterial growth. {ECO:0000269|PubMed:12453413}.;

Recessive Scores

pRec: 0.647

Intolerance Scores

LoFtool: 0.730
RVIS EVS: 0.84
RVIS percentile EVS: 88.23

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.978

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium