LCN6

Summary

LCN6 (lipocalin 6, HGNC:17337) is a protein-coding gene on chromosome 9q34.3, encoding Epididymal-specific lipocalin-6 (P62502). May play a role in male fertility.

Predicted to enable small molecule binding activity. Predicted to be involved in single fertilization. Predicted to act upstream of or within several processes, including acrosome reaction; calcium ion homeostasis; and response to calcium ion. Predicted to be located in extracellular region.

Source: NCBI Gene 158062 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 44 total
• MANE Select transcript: NM_198946

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17337
Approved symbol	LCN6
Name	lipocalin 6
Location	9q34.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000267206
Ensembl biotype	protein_coding
OMIM	609379
Entrez	158062

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding_CDS_not_defined, 3 protein_coding

ENST00000341206, ENST00000471509, ENST00000476567, ENST00000480347, ENST00000494091, ENST00000497749, ENST00000960388

RefSeq mRNA: 1 — MANE Select: NM_198946 NM_198946

CCDS: CCDS7005

Canonical transcript exons

ENST00000341206 — 7 exons

Exon	Start	End
ENSE00001386798	136744017	136744142
ENSE00001388943	136748394	136748525
ENSE00003519861	136744339	136744364
ENSE00003586429	136745844	136745914
ENSE00003658827	136745170	136745280
ENSE00003687613	136747424	136747563
ENSE00003688897	136744640	136744741

Expression profiles

Bgee: expression breadth ubiquitous, 148 present calls, max score 95.69.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4701 / max 377.8064, expressed in 78 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
103200	0.2974	14
103198	0.0848	32
103197	0.0336	16
103196	0.0317	18
103199	0.0226	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	95.69	gold quality
left uterine tube	UBERON:0001303	94.59	gold quality
mucosa of stomach	UBERON:0001199	94.48	gold quality
body of uterus	UBERON:0009853	92.19	gold quality
heart left ventricle	UBERON:0002084	89.72	gold quality
endocervix	UBERON:0000458	88.84	gold quality
cardiac ventricle	UBERON:0002082	88.75	gold quality
left coronary artery	UBERON:0001626	86.59	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	86.41	gold quality
lower esophagus muscularis layer	UBERON:0035833	86.30	gold quality
lower esophagus	UBERON:0013473	86.12	gold quality
tibial nerve	UBERON:0001323	85.61	gold quality
right coronary artery	UBERON:0001625	85.48	gold quality
right ovary	UBERON:0002118	84.28	gold quality
coronary artery	UBERON:0001621	84.01	gold quality
right atrium auricular region	UBERON:0006631	83.94	gold quality
body of stomach	UBERON:0001161	83.73	gold quality
heart	UBERON:0000948	83.52	gold quality
cardiac atrium	UBERON:0002081	82.84	gold quality
ectocervix	UBERON:0012249	82.83	gold quality
smooth muscle tissue	UBERON:0001135	82.60	gold quality
small intestine Peyer’s patch	UBERON:0003454	82.57	gold quality
omental fat pad	UBERON:0010414	82.57	gold quality
peritoneum	UBERON:0002358	82.45	gold quality
left ovary	UBERON:0002119	81.69	gold quality
right lung	UBERON:0002167	80.67	gold quality
minor salivary gland	UBERON:0001830	80.32	gold quality
subcutaneous adipose tissue	UBERON:0002190	80.30	gold quality
adipose tissue of abdominal region	UBERON:0007808	80.28	gold quality
esophagus	UBERON:0001043	80.24	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-HCAD-38	yes	5829.45
E-MTAB-10287	yes	78.58
E-GEOD-134144	yes	52.68
E-HCAD-4	yes	49.65
E-HCAD-6	yes	45.27
E-ANND-3	yes	12.90
E-MTAB-9067	yes	11.49

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

2 targeting LCN6, 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-4303	98.01	68.13	2304
HSA-MIR-4790-5P	96.67	67.45	167

Literature-anchored findings (GeneRIF, showing 2)

• Predominant expression in the epididymis and location on sperm surface are consistent with a role for LCN6 in male fertility (PMID:14617364)
• Anti-hLCN6 Monoclonal Antibody. (PMID:29053426)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Lcn6	ENSMUSG00000045684
rattus_norvegicus	Lcn6	ENSRNOG00000028095

Paralogs (12): PTGDS (ENSG00000107317), PAEP (ENSG00000122133), OBP2A (ENSG00000122136), LCN2 (ENSG00000148346), LCN9 (ENSG00000148386), LCN1 (ENSG00000160349), OBP2B (ENSG00000171102), LCN15 (ENSG00000177984), LCN12 (ENSG00000184925), LCN10 (ENSG00000187922), LCN8 (ENSG00000204001), LCNL1 (ENSG00000214402)

Protein

Protein identifiers

Epididymal-specific lipocalin-6 — P62502 (reviewed: P62502)

Alternative names: Lipocalin-5

All UniProt accessions (3): A0A024R8I9, P62502, K7ERN5

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in male fertility.

Subcellular location. Secreted.

Tissue specificity. Predominantly expressed in epididymis.

Similarity. Belongs to the calycin superfamily. Lipocalin family.

RefSeq proteins (1): NP_945184* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF00061

UniProt features (2 total): signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P62502-F1	80.09	0.45

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 24 (showing top): GOBP_SINGLE_FERTILIZATION, GOBP_RESPONSE_TO_METAL_ION, GOBP_ANATOMICAL_STRUCTURE_MATURATION, GOBP_CELL_MATURATION, GOBP_MONOATOMIC_ION_HOMEOSTASIS, GOBP_ACROSOME_REACTION, GOBP_FERTILIZATION, GOBP_RESPONSE_TO_CALCIUM_ION, GOBP_HOMEOSTATIC_PROCESS, GOBP_CHEMICAL_HOMEOSTASIS, CAMPS_COLON_CANCER_COPY_NUMBER_UP, E2F3_UP.V1_UP, chr9q34, GOBP_DEVELOPMENTAL_MATURATION, HAY_BONE_MARROW_CD34_POS_PRE_PC

GO Biological Process (6): acrosome reaction (GO:0007340), cellular homeostasis (GO:0019725), cell maturation (GO:0048469), response to calcium ion (GO:0051592), calcium ion homeostasis (GO:0055074), single fertilization (GO:0007338)

GO Molecular Function (1): small molecule binding (GO:0036094)

GO Cellular Component (1): extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
membrane fusion involved in acrosome reaction	1
single fertilization	1
reproductive process	1
acrosomal vesicle exocytosis	1
homeostatic process	1
cell development	1
cellular developmental process	1
anatomical structure maturation	1
response to metal ion	1
monoatomic cation homeostasis	1
inorganic ion homeostasis	1
fertilization	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

590 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LCN6	LCN8	Q6JVE9	763
LCN6	LCN10	Q6JVE6	726
LCN6	LCN9	Q8WX39	716
LCN6	LCN12	Q6JVE5	588
LCN6	Q5T8A5	Q5T8A5	576
LCN6	TEDDM1	Q5T9Z0	576
LCN6	LCN1	P31025	570
LCN6	CST11	Q9H112	538
LCN6	LCNL1	Q6ZST4	506
LCN6	OBP2B	Q9NPH6	441
LCN6	DEFB128	Q7Z7B8	438
LCN6	PRSS45P	Q7RTY3	427
LCN6	WDR97	A6NE52	419
LCN6	BSPH1	Q075Z2	403
LCN6	SPINT4	Q6UDR6	401

IntAct

4 interactions, top by confidence:

A	B	Type	Score
LCN6	COCH	psi-mi:“MI:0914”(association)	0.350
LCN6	POTEF	psi-mi:“MI:0914”(association)	0.350
LCN6	HIGD1C	psi-mi:“MI:0914”(association)	0.350

BioGRID (67): UGDH (Affinity Capture-MS), HS6ST2 (Affinity Capture-MS), GPC4 (Affinity Capture-MS), CERCAM (Affinity Capture-MS), C15orf39 (Affinity Capture-MS), KDELC1 (Affinity Capture-MS), SEMA4D (Affinity Capture-MS), RTN4RL2 (Affinity Capture-MS), FOXRED2 (Affinity Capture-MS), LMLN (Affinity Capture-MS), ENPP1 (Affinity Capture-MS), MAN2B2 (Affinity Capture-MS), ITGA4 (Affinity Capture-MS), CHST12 (Affinity Capture-MS), CHST7 (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: P62502, P62503

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	32
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1449 predictions. Top by Δscore:

Variant	Effect	Δscore
9:136744365:C:CC	acceptor_gain	1.0000
9:136744638:A:AC	donor_gain	1.0000
9:136744639:C:CC	donor_gain	1.0000
9:136744639:CGGT:C	donor_gain	1.0000
9:136744759:G:GC	acceptor_gain	1.0000
9:136745163:CACT:C	donor_loss	1.0000
9:136745164:ACTT:A	donor_loss	1.0000
9:136745166:TTA:T	donor_loss	1.0000
9:136745167:TACT:T	donor_loss	1.0000
9:136745168:A:AC	donor_gain	1.0000
9:136745169:C:CA	donor_gain	1.0000
9:136745169:C:CT	donor_gain	1.0000
9:136745169:C:T	donor_loss	1.0000
9:136745169:CTGT:C	donor_gain	1.0000
9:136745169:CTGTA:C	donor_gain	1.0000
9:136745278:TTG:T	acceptor_gain	1.0000
9:136745281:C:CC	acceptor_gain	1.0000
9:136748388:CTGTA:C	donor_loss	1.0000
9:136748390:GTACC:G	donor_loss	1.0000
9:136748393:C:CT	donor_loss	1.0000
9:136744638:ACGGT:A	donor_gain	0.9900
9:136744639:CGGTC:C	donor_gain	0.9900
9:136744752:C:CT	acceptor_gain	0.9900
9:136744753:A:T	acceptor_gain	0.9900
9:136744757:CAG:C	acceptor_gain	0.9900
9:136744759:G:C	acceptor_gain	0.9900
9:136745169:CT:C	donor_gain	0.9900
9:136745169:CTG:C	donor_gain	0.9900
9:136745276:TATTG:T	acceptor_gain	0.9900
9:136745277:ATTG:A	acceptor_gain	0.9900

AlphaMissense

1047 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:136745854:A:C	F97L	0.915
9:136745854:A:T	F97L	0.915
9:136745856:A:G	F97L	0.915
9:136744674:G:C	F160L	0.889
9:136744674:G:T	F160L	0.889
9:136744676:A:G	F160L	0.889
9:136744701:G:C	F151L	0.886
9:136744701:G:T	F151L	0.886
9:136744703:A:G	F151L	0.886
9:136747513:A:C	F47L	0.883
9:136747513:A:T	F47L	0.883
9:136747515:A:G	F47L	0.883
9:136745240:G:C	F114L	0.842
9:136745240:G:T	F114L	0.842
9:136745242:A:G	F114L	0.842
9:136745189:G:C	F131L	0.806
9:136745189:G:T	F131L	0.806
9:136745191:A:G	F131L	0.806
9:136744740:A:C	S138R	0.785
9:136744740:A:T	S138R	0.785
9:136745170:T:G	S138R	0.785
9:136744689:G:C	S155R	0.761
9:136744689:G:T	S155R	0.761
9:136744691:T:G	S155R	0.761
9:136744702:A:C	F151C	0.755
9:136745219:G:C	F121L	0.753
9:136745219:G:T	F121L	0.753
9:136745221:A:G	F121L	0.753
9:136744675:A:G	F160S	0.741
9:136745226:A:C	I119S	0.725

dbSNP variants (sampled 300 via entrez): RS1000540096 (9:136747040 G>A,C), RS1001016722 (9:136747233 G>C,T), RS1001710956 (9:136747303 G>A,C,T), RS1002314179 (9:136747626 CCCTCCAGCCTCAG>C), RS1002678168 (9:136744670 A>G,T), RS1003275383 (9:136749604 G>A,C), RS1003826414 (9:136748570 C>A,T), RS1003910564 (9:136743570 A>G), RS1003931410 (9:136744126 T>G), RS1004678913 (9:136746824 C>T), RS1005386465 (9:136749016 C>T), RS1005496093 (9:136744272 G>A), RS1005568215 (9:136744460 C>T), RS1005770384 (9:136748814 C>T), RS1006349906 (9:136747830 C>T)

Disease associations

OMIM: gene MIM:609379 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST009597_181	Multiple sclerosis	7.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Tretinoin	decreases expression	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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