LCN1

protein-coding

lipocalin 1, the group of Lipocalins

Gene summary

This gene encodes a member of the lipocalin family of small secretory proteins. Lipocalins are extracellular transport proteins that bind to a variety of hydrophobic ligands. The encoded protein is the primary lipid binding protein in tears and is overproduced in response to multiple stimuli including infection and stress. The encoded protein may be a marker for chromosome aneuploidy as well as an autoantigen in Sjogren's syndrome. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and two pseudogenes of this gene are also located on the long arm of chromosome 9. [provided by RefSeq, Nov 2011]

MANE transcript

NM_002297.4

Inheritance

—

ClinVar variants

U:40B:5

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.21

Max pathogenic AF

—

Genomic locus

chr9:135,521,438-135,526,540

External References & Databases

Ensembl (ENSG00000160349)

Transcript & Mutation Effects

hg38 • Region Span ~5.1 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 LCN1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 40

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002297.4. 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 clinvar	1 clinvar	3
missense			39 clinvar	2 clinvar	1 clinvar	42
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	40	3	2	45

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 9 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002297.4	RefSeq	NP_002288.1	6	MANE Select
ENST00000371781.4	Ensembl	ENSP00000360846.3	6	MANE Select
NM_001252617.2	RefSeq	NP_001239546.1	6	Standard
NM_001252618.2	RefSeq	NP_001239547.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Transport of fatty acids
Transport of vitamins, nucleosides, and related molecules
SLC-mediated transmembrane transport
Transport of small molecules

Biological Process

retina homeostasis
proteolysis
negative regulation of endopeptidase activity
long-chain fatty acid transport
response to stimulus

Molecular Function

cysteine-type endopeptidase inhibitor activity
signaling receptor binding
zinc ion binding
chloride ion binding
small molecule binding

Cellular Component

extracellular region
extracellular space

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000263598
Coding exons: 6
Length: 5095
Individuals with no LoFs: 125660
Homozygous LoFs: 0
Heterozygous LoFs: 71
Defined: 125731
p: 0.000282

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.763	130	108	1.21	0.00000683	1120
Missense (PolyPhen)		25	21.718	1.1511		308
Synonymous	0.142	47	48.3	0.974	0.00000368	339
Loss of Function	-0.583	11	9.10	1.21	4.70e-7	115

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00037	0.00037	rare
Latino/Admixed American	0.00026	0.00026	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00058	0.00054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00038	0.00037	rare
South Asian	0.000098	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Could play a role in taste reception. Could be necessary for the concentration and delivery of sapid molecules in the gustatory system. Can bind various ligands, with chemical structures ranging from lipids and retinoids to the macrocyclic antibiotic rifampicin and even to microbial siderophores. Exhibits an extremely wide ligand pocket.;

Recessive Scores

pRec: 0.125

Intolerance Scores

LoFtool: 0.820
RVIS EVS: 0.22
RVIS percentile EVS: 68.27

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.682

Gene Damage Prediction

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