LCN8

Summary

LCN8 (lipocalin 8, HGNC:27038) is a protein-coding gene on chromosome 9q34.3, encoding Epididymal-specific lipocalin-8 (Q6JVE9). May play a role in male fertility.

Members of the lipocalin family, such as LCN8, have a common structure consisting of an 8-stranded antiparallel beta-barrel that forms a cup-shaped ligand-binding pocket or calyx. Lipocalins generally bind small hydrophobic ligands and transport them to specific cells (Suzuki et al., 2004 [PubMed 15363845]).

Source: NCBI Gene 138307 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 43 total
• MANE Select transcript: NM_178469

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27038
Approved symbol	LCN8
Name	lipocalin 8
Location	9q34.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000204001
Ensembl biotype	protein_coding
OMIM	612902
Entrez	138307

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000371688, ENST00000479767, ENST00000480597, ENST00000482893, ENST00000612714, ENST00000966428

RefSeq mRNA: 2 — MANE Select: NM_178469 NM_001345934, NM_178469

CCDS: CCDS35183, CCDS87717

Canonical transcript exons

ENST00000371688 — 7 exons

Exon	Start	End
ENSE00001455864	136755412	136755516
ENSE00001455866	136757907	136758243
ENSE00001771914	136757038	136757168
ENSE00003463919	136756522	136756592
ENSE00003527718	136755244	136755333
ENSE00003537978	136754386	136754509
ENSE00003624642	136755135	136755160

Expression profiles

Bgee: expression breadth ubiquitous, 102 present calls, max score 92.59.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1666 / max 139.6104, expressed in 25 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
103202	0.0446	10
103209	0.0379	6
103201	0.0156	6
103204	0.0150	2
103206	0.0125	3
103210	0.0067	2
103203	0.0063	4
103207	0.0062	1
103211	0.0061	4
205688	0.0051	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	92.59	gold quality
right hemisphere of cerebellum	UBERON:0014890	85.55	gold quality
cerebellar hemisphere	UBERON:0002245	85.12	gold quality
cerebellar cortex	UBERON:0002129	84.96	gold quality
cerebellum	UBERON:0002037	83.30	gold quality
caput epididymis	UBERON:0004358	72.97	gold quality
myocardium	UBERON:0002349	66.86	gold quality
hindlimb stylopod muscle	UBERON:0004252	66.22	gold quality
cerebellar vermis	UBERON:0004720	63.50	gold quality
gastrocnemius	UBERON:0001388	61.81	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	61.19	gold quality
muscle of leg	UBERON:0001383	61.01	gold quality
cauda epididymis	UBERON:0004360	60.02	gold quality
esophagus squamous epithelium	UBERON:0006920	58.67	gold quality
cartilage tissue	UBERON:0002418	58.20	gold quality
thyroid gland	UBERON:0002046	58.16	gold quality
right lobe of thyroid gland	UBERON:0001119	57.82	gold quality
left lobe of thyroid gland	UBERON:0001120	57.25	gold quality
skeletal muscle tissue	UBERON:0001134	56.69	gold quality
thymus	UBERON:0002370	56.65	gold quality
Brodmann (1909) area 46	UBERON:0006483	56.43	gold quality
gingiva	UBERON:0001828	55.97	gold quality
lymph node	UBERON:0000029	55.62	gold quality
superficial temporal artery	UBERON:0001614	54.85	gold quality
gingival epithelium	UBERON:0001949	54.61	gold quality
ventral tegmental area	UBERON:0002691	54.16	gold quality
right frontal lobe	UBERON:0002810	54.09	gold quality
subthalamic nucleus	UBERON:0001906	54.08	gold quality
trigeminal ganglion	UBERON:0001675	54.07	gold quality
heart right ventricle	UBERON:0002080	53.96	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-HCAD-38	yes	2325.21
E-ANND-3	no	1.05

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, FOXA2, GATA3

miRNA regulators (miRDB)

14 targeting LCN8, 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-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-892C-5P	99.16	70.56	2116
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-6501-3P	98.71	67.45	1480
HSA-MIR-3661	97.83	67.30	705
HSA-MIR-3665	97.73	65.08	975
HSA-MIR-4456	97.50	64.88	1678
HSA-MIR-631	97.05	66.93	602
HSA-MIR-541-3P	96.07	66.11	1271
HSA-MIR-654-5P	96.07	66.18	1280

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Lcn8	ENSMUSG00000036449
rattus_norvegicus	Lcn8	ENSRNOG00000017161

Paralogs (12): PTGDS (ENSG00000107317), PAEP (ENSG00000122133), OBP2A (ENSG00000122136), LCN2 (ENSG00000148346), LCN9 (ENSG00000148386), LCN1 (ENSG00000160349), OBP2B (ENSG00000171102), LCN15 (ENSG00000177984), LCN12 (ENSG00000184925), LCN10 (ENSG00000187922), LCNL1 (ENSG00000214402), LCN6 (ENSG00000267206)

Protein

Protein identifiers

Epididymal-specific lipocalin-8 — Q6JVE9 (reviewed: Q6JVE9)

All UniProt accessions (2): A0A384MDK0, Q6JVE9

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in male fertility. May act as a retinoid carrier protein within the epididymis.

Subcellular location. Secreted.

Similarity. Belongs to the calycin superfamily. Lipocalin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6JVE9-1	1	yes
Q6JVE9-2	2

RefSeq proteins (2): NP_001332863, NP_848564* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF00061

UniProt features (6 total): glycosylation site 2, signal peptide 1, chain 1, disulfide bond 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6JVE9-F1	81.57	0.52

Functional residue map

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

Disulfide bonds (1): 79–166

Glycosylation sites (2): 66, 74

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 41 (showing top): GOBP_RESPONSE_TO_HORMONE, CAMPS_COLON_CANCER_COPY_NUMBER_UP, MIKKELSEN_MEF_LCP_WITH_H3K27ME3, MARTENS_TRETINOIN_RESPONSE_UP, chr9q34, ADCYAP1_TARGET_GENES, RYBP_TARGET_GENES, SFMBT1_TARGET_GENES, ZNF563_TARGET_GENES, ZNF618_TARGET_GENES, ZNF768_TARGET_GENES, GSE10240_IL22_VS_IL22_AND_IL17_STIM_PRIMARY_BRONCHIAL_EPITHELIAL_CELLS_UP, GSE13306_RA_VS_UNTREATED_TREG_DN, SAFB2_TARGET_GENES, GSE17721_CTRL_VS_POLYIC_4H_BMDC_DN

GO Biological Process (1): response to hormone (GO:0009725)

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
response to endogenous stimulus	1
response to chemical	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

456 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LCN8	LCN6	P62502	763
LCN8	LCN9	Q8WX39	751
LCN8	Q5T8A5	Q5T8A5	679
LCN8	LCN10	Q6JVE6	662
LCN8	LCN12	Q6JVE5	592
LCN8	CST11	Q9H112	587
LCN8	LCN1	P31025	578
LCN8	TEDDM1	Q5T9Z0	557
LCN8	LCN15	Q6UWW0	555
LCN8	OBP2B	Q9NPH6	523
LCN8	LCNL1	Q6ZST4	511
LCN8	APOD	P05090	494
LCN8	CST8	O60676	483
LCN8	RNASE10	Q5GAN6	449
LCN8	BRSK1	Q8TDC3	448

IntAct

3 interactions, top by confidence:

A	B	Type	Score
ECE1	LCN8	psi-mi:“MI:0915”(physical association)	0.370
LCN8	LRRC41	psi-mi:“MI:0914”(association)	0.350

BioGRID (9): FAHD2A (Affinity Capture-MS), MKS1 (Affinity Capture-MS), THRSP (Affinity Capture-MS), WDR45 (Affinity Capture-MS), NUB1 (Affinity Capture-MS), LRRC41 (Affinity Capture-MS), GFM2 (Affinity Capture-MS), LCN8 (Proximity Label-MS), LCN8 (Positive Genetic)

ESM2 similar proteins: B3EY83, B5X0G2, O02853, O09114, O18873, O97921, P02754, P02758, P04119, P07360, P07380, P09466, P11672, P13613, P19647, P21664, P21760, P22057, P30152, P31025, P33685, P33686, P33687, P33688, P41222, P53715, P62502, P62503, P67975, P67976, P80188, Q01584, Q28679, Q29095, Q29487, Q29562, Q5VSP4, Q6JVE6, Q6JVE9, Q6JVL5

Diamond homologs: Q6JVE9, Q924P3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	34
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1367 predictions. Top by Δscore:

Variant	Effect	Δscore
9:136755410:A:AC	donor_gain	1.0000
9:136755411:C:CC	donor_gain	1.0000
9:136755418:A:AC	donor_gain	1.0000
9:136755419:C:CC	donor_gain	1.0000
9:136755421:TGAGG:T	donor_gain	1.0000
9:136757033:CTTAC:C	donor_loss	1.0000
9:136757034:TTA:T	donor_loss	1.0000
9:136757036:A:AG	donor_loss	1.0000
9:136757037:C:CA	donor_loss	1.0000
9:136755238:GCTCA:G	donor_loss	0.9900
9:136755239:CT:C	donor_loss	0.9900
9:136755240:TCA:T	donor_loss	0.9900
9:136755241:CAC:C	donor_loss	0.9900
9:136755242:ACCAG:A	donor_loss	0.9900
9:136755243:C:CA	donor_loss	0.9900
9:136755436:T:A	donor_gain	0.9900
9:136755528:G:T	acceptor_gain	0.9900
9:136755531:C:CT	acceptor_gain	0.9900
9:136756588:CTGAG:C	acceptor_gain	0.9900
9:136756593:C:CC	acceptor_gain	0.9900
9:136757036:A:AC	donor_gain	0.9900
9:136757037:C:CC	donor_gain	0.9900
9:136757888:A:AC	donor_gain	0.9900
9:136757889:C:CC	donor_gain	0.9900
9:136754926:C:A	donor_gain	0.9800
9:136755161:C:CC	acceptor_gain	0.9800
9:136755237:GGCTC:G	donor_loss	0.9800
9:136755243:CCAGG:C	donor_gain	0.9800
9:136755532:A:C	acceptor_gain	0.9800
9:136755536:C:CT	acceptor_gain	0.9800

AlphaMissense

975 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:136757157:G:C	F35L	0.980
9:136757157:G:T	F35L	0.980
9:136757159:A:G	F35L	0.980
9:136756532:G:C	F95L	0.979
9:136756532:G:T	F95L	0.979
9:136756534:A:G	F95L	0.979
9:136755290:A:C	F148L	0.972
9:136755290:A:T	F148L	0.972
9:136755292:A:G	F148L	0.972
9:136756526:A:C	F97L	0.971
9:136756526:A:T	F97L	0.971
9:136756528:A:G	F97L	0.971
9:136757154:C:A	W36C	0.965
9:136757154:C:G	W36C	0.965
9:136756527:A:C	F97C	0.955
9:136755291:A:C	F148C	0.954
9:136757156:A:G	W36R	0.952
9:136757156:A:T	W36R	0.952
9:136755291:A:G	F148S	0.951
9:136756527:A:G	F97S	0.938
9:136757137:G:T	A42D	0.935
9:136755431:A:C	F127L	0.931
9:136755431:A:T	F127L	0.931
9:136755433:A:G	F127L	0.931
9:136755418:A:G	Y132H	0.925
9:136755468:A:G	I115T	0.925
9:136755472:C:G	A114P	0.925
9:136757158:A:C	F35C	0.925
9:136757093:C:G	G57R	0.924
9:136755418:A:C	Y132D	0.923

dbSNP variants (sampled 300 via entrez): RS1000155056 (9:136755440 G>C,T), RS1000491068 (9:136756876 G>A), RS1001904860 (9:136758082 G>A,C), RS1002880265 (9:136757062 A>C,G), RS1003066786 (9:136759788 G>A), RS1003190536 (9:136754325 G>A,T), RS1003205988 (9:136759139 G>A), RS1003264459 (9:136754532 C>T), RS1003549945 (9:136759453 GC>G), RS1004092532 (9:136754705 G>T), RS1004488980 (9:136757475 G>A,C,T), RS1005115808 (9:136758010 G>A,C), RS1005207858 (9:136754697 C>T), RS1006083830 (9:136758126 G>A,C), RS1006718443 (9:136757342 C>A)

Disease associations

OMIM: gene MIM:612902 | 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)

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects response to substance, increases expression, affects methylation, increases methylation	3
Aflatoxin B1	decreases methylation	2
aflatoxin B2	decreases methylation	1
Arsenic	decreases methylation	1
Phthalic Acids	increases methylation	1
Silicon Dioxide	decreases expression	1
Valproic Acid	increases methylation	1
Cadmium Chloride	increases expression	1

Clinical trials (associated diseases)

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