LCN12

Summary

LCN12 (lipocalin 12, HGNC:28733) is a protein-coding gene on chromosome 9q34.3, encoding Epididymal-specific lipocalin-12 (Q6JVE5). Binds all-trans retinoic acid and may act as a retinoid carrier protein within the epididymis.

Members of the lipocalin family, such as LCN12, 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 286256 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Tourette syndrome (No Known Disease Relationship, GenCC)
• GWAS associations: 5
• Clinical variants (ClinVar): 44 total
• MANE Select transcript: NM_178536

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28733
Approved symbol	LCN12
Name	lipocalin 12
Location	9q34.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC48935
Ensembl gene	ENSG00000184925
Ensembl biotype	protein_coding
OMIM	612905
Entrez	286256

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 11 protein_coding_CDS_not_defined, 5 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000371632, ENST00000371633, ENST00000463714, ENST00000466277, ENST00000470501, ENST00000471615, ENST00000476751, ENST00000480204, ENST00000484304, ENST00000491316, ENST00000491603, ENST00000492820, ENST00000494713, ENST00000495410, ENST00000496895, ENST00000874069, ENST00000874070, ENST00000961465

RefSeq mRNA: 1 — MANE Select: NM_178536 NM_178536

CCDS: CCDS7018

Canonical transcript exons

ENST00000371633 — 6 exons

Exon	Start	End
ENSE00001867817	136952273	136952441
ENSE00001904980	136955371	136955497
ENSE00003471714	136953848	136953964
ENSE00003504296	136953700	136953779
ENSE00003548609	136952892	136953028
ENSE00003612136	136954154	136954255

Expression profiles

Bgee: expression breadth ubiquitous, 190 present calls, max score 99.25.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.0949 / max 706.2153, expressed in 131 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
99593	0.6947	52
99596	0.2342	91
99595	0.0732	44
99597	0.0511	36
99598	0.0226	7
99594	0.0190	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	99.25	gold quality
left lobe of thyroid gland	UBERON:0001120	98.87	gold quality
corpus epididymis	UBERON:0004359	98.78	gold quality
right lobe of thyroid gland	UBERON:0001119	98.61	gold quality
thyroid gland	UBERON:0002046	97.90	gold quality
right lobe of liver	UBERON:0001114	95.23	gold quality
metanephros cortex	UBERON:0010533	92.60	gold quality
adenohypophysis	UBERON:0002196	91.53	gold quality
cauda epididymis	UBERON:0004360	91.12	gold quality
pituitary gland	UBERON:0000007	90.75	gold quality
left uterine tube	UBERON:0001303	88.77	gold quality
caput epididymis	UBERON:0004358	86.69	gold quality
right testis	UBERON:0004534	86.48	gold quality
endocervix	UBERON:0000458	86.07	gold quality
caudate nucleus	UBERON:0001873	85.60	gold quality
right atrium auricular region	UBERON:0006631	85.52	gold quality
spleen	UBERON:0002106	85.38	gold quality
left testis	UBERON:0004533	85.38	gold quality
putamen	UBERON:0001874	85.33	gold quality
adult mammalian kidney	UBERON:0000082	85.21	gold quality
nucleus accumbens	UBERON:0001882	84.42	gold quality
apex of heart	UBERON:0002098	84.22	gold quality
cardiac atrium	UBERON:0002081	84.19	gold quality
amygdala	UBERON:0001876	83.74	gold quality
liver	UBERON:0002107	83.58	gold quality
fallopian tube	UBERON:0003889	83.55	gold quality
metanephros	UBERON:0000081	83.47	gold quality
right frontal lobe	UBERON:0002810	83.47	gold quality
cortex of kidney	UBERON:0001225	83.32	gold quality
testis	UBERON:0000473	83.00	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-HCAD-38	no	3644.11
E-ANND-3	no	1.21

Regulation

Is transcription factor: no

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
mus_musculus	Lcn12	ENSMUSG00000026943

Paralogs (12): PTGDS (ENSG00000107317), PAEP (ENSG00000122133), OBP2A (ENSG00000122136), LCN2 (ENSG00000148346), LCN9 (ENSG00000148386), LCN1 (ENSG00000160349), OBP2B (ENSG00000171102), LCN15 (ENSG00000177984), LCN10 (ENSG00000187922), LCN8 (ENSG00000204001), LCNL1 (ENSG00000214402), LCN6 (ENSG00000267206)

Protein

Protein identifiers

Epididymal-specific lipocalin-12 — Q6JVE5 (reviewed: Q6JVE5)

All UniProt accessions (4): Q6JVE5, A0A384MDV4, Q5SQ16, R4GN38

UniProt curated annotations — full annotation on UniProt →

Function. Binds all-trans retinoic acid and may act as a retinoid carrier protein within the epididymis. May play a role in male fertility.

Subunit / interactions. Monomer.

Subcellular location. Secreted.

Similarity. Belongs to the calycin superfamily. Lipocalin family.

RefSeq proteins (1): NP_848631* (*=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 (3 total): signal peptide 1, chain 1, disulfide bond 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6JVE5-F1	86.62	0.64

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): 88–192

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-804914	Transport of fatty acids
R-HSA-382551	Transport of small molecules
R-HSA-425397	Transport of vitamins, nucleosides, and related molecules
R-HSA-425407	SLC-mediated transmembrane transport

MSigDB gene sets: 33 (showing top): GOMF_RETINOIC_ACID_BINDING, GOMF_ISOPRENOID_BINDING, GOMF_ORGANIC_ACID_BINDING, GOMF_LIPID_BINDING, GOMF_MONOCARBOXYLIC_ACID_BINDING, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, REACTOME_TRANSPORT_OF_SMALL_MOLECULES, REACTOME_TRANSPORT_OF_FATTY_ACIDS, chr9q34, DESCARTES_FETAL_KIDNEY_URETERIC_BUD_CELLS, OSMAN_BLOOD_CHAD63_KH_AGE_18_50YO_HIGH_DOSE_SUBJECTS_24HR_DN, GSE29615_CTRL_VS_DAY3_LAIV_IFLU_VACCINE_PBMC_DN, GSE29615_CTRL_VS_LAIV_FLU_VACCINE_PBMC_DN, GSE32423_CTRL_VS_IL7_MEMORY_CD8_TCELL_DN, GSE32423_CTRL_VS_IL7_IL4_MEMORY_CD8_TCELL_DN

GO Biological Process (0):

GO Molecular Function (2): retinoic acid binding (GO:0001972), small molecule binding (GO:0036094)

GO Cellular Component (2): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Transport of vitamins, nucleosides, and related molecules	1
SLC-mediated transmembrane transport	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
retinoid binding	1
monocarboxylic acid binding	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

396 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LCN12	LCN9	Q8WX39	619
LCN12	Q5T8A5	Q5T8A5	609
LCN12	LCN10	Q6JVE6	606
LCN12	LCN8	Q6JVE9	592
LCN12	CCDC183	Q5T5S1	589
LCN12	LCN6	P62502	588
LCN12	TMEM248	Q9NWD8	581
LCN12	TMEM141	Q96I45	577
LCN12	MAMDC4	Q6UXC1	552
LCN12	ZNF469	Q96JG9	506
LCN12	VKORC1L1	Q8N0U8	505
LCN12	OBP2B	Q9NPH6	480
LCN12	LCN15	Q6UWW0	470
LCN12	NPDC1	Q9NQX5	470
LCN12	GLT8D2	Q9H1C3	453

IntAct

3 interactions, top by confidence:

A	B	Type	Score
LCN12	HSPA5	psi-mi:“MI:0915”(physical association)	0.400
MYC		psi-mi:“MI:0914”(association)	0.350

BioGRID (2): LCN12 (Affinity Capture-MS), HSPA5 (Affinity Capture-MS)

ESM2 similar proteins: O00292, O02853, O09114, O18796, O75610, O97921, P07360, P07380, P11672, P19647, P21664, P22057, P30152, P41222, P57785, P62502, P62503, P67976, P80188, Q06643, Q06AS9, Q28679, Q29095, Q29487, Q29562, Q5T7M4, Q5TM22, Q63148, Q64280, Q6JVE5, Q6JVE6, Q6JVE9, Q6JVL5, Q6UXF7, Q6UXT9, Q6ZMM2, Q810Z1, Q862Z7, Q86WI3, Q86YD3

Diamond homologs: B3EY83, P11672, P30152, P80188, Q6JVE5, Q6JVL5, O02853, O09114, O97921, P22057, P41222, Q01584, Q29095, Q29487, Q29562, Q6UWW0, Q8WNM0, Q8WNM1, Q9TUI1, Q9XS65, Q9XSM0, P00978, Q07456, Q60559, Q64240, Q9I9P7

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	31
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

867 predictions. Top by Δscore:

Variant	Effect	Δscore
9:136952887:TGTAG:T	acceptor_loss	0.9700
9:136952888:GTA:G	acceptor_loss	0.9700
9:136952889:TAGTT:T	acceptor_loss	0.9700
9:136952891:G:A	acceptor_loss	0.9700
9:136953846:A:AG	acceptor_gain	0.9700
9:136953847:G:GG	acceptor_gain	0.9700
9:136952890:A:AG	acceptor_gain	0.9600
9:136952891:G:GG	acceptor_gain	0.9600
9:136953599:G:A	acceptor_gain	0.9600
9:136952985:C:G	donor_gain	0.9500
9:136953598:T:TA	acceptor_gain	0.9300
9:136953631:G:GC	acceptor_gain	0.9300
9:136952437:ACCAG:A	donor_loss	0.9200
9:136952438:CCAGG:C	donor_loss	0.9200
9:136952439:CAG:C	donor_loss	0.9200
9:136952440:AG:A	donor_loss	0.9200
9:136952441:GGTAC:G	donor_loss	0.9200
9:136952442:GT:G	donor_loss	0.9200
9:136952443:T:G	donor_loss	0.9200
9:136953847:GA:G	acceptor_gain	0.9000
9:136953029:G:GG	donor_gain	0.8900
9:136952434:G:GT	donor_gain	0.8800
9:136953027:CG:C	donor_loss	0.8600
9:136953028:GGTGA:G	donor_loss	0.8600
9:136953029:GTGAG:G	donor_loss	0.8600
9:136953030:TGA:T	donor_loss	0.8600
9:136953032:AG:A	donor_loss	0.8600
9:136953732:T:A	acceptor_gain	0.8600
9:136953033:G:T	donor_loss	0.8500
9:136953697:CAG:C	acceptor_gain	0.8500

AlphaMissense

1247 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:136952904:T:A	W43R	0.983
9:136952904:T:C	W43R	0.983
9:136952906:G:C	W43C	0.983
9:136952906:G:T	W43C	0.983
9:136953758:T:C	F104L	0.983
9:136953760:C:A	F104L	0.983
9:136953760:C:G	F104L	0.983
9:136952893:T:G	F39C	0.981
9:136952967:T:C	F64L	0.981
9:136952969:C:A	F64L	0.981
9:136952969:C:G	F64L	0.981
9:136954192:T:C	F163L	0.977
9:136954194:C:A	F163L	0.977
9:136954194:C:G	F163L	0.977
9:136953721:G:C	W91C	0.973
9:136953721:G:T	W91C	0.973
9:136953901:T:C	F129L	0.972
9:136953903:C:A	F129L	0.972
9:136953903:C:G	F129L	0.972
9:136952892:T:C	F39L	0.971
9:136952894:C:A	F39L	0.971
9:136952894:C:G	F39L	0.971
9:136954193:T:G	F163C	0.971
9:136954193:T:C	F163S	0.970
9:136952427:T:C	F34L	0.969
9:136952428:T:G	F34C	0.969
9:136952429:C:A	F34L	0.969
9:136952429:C:G	F34L	0.969
9:136953759:T:C	F104S	0.969
9:136953886:A:C	S124R	0.969

dbSNP variants (sampled 300 via entrez): RS1000431990 (9:136956981 G>T), RS1000661052 (9:136950229 A>G), RS1000671889 (9:136955975 G>A), RS1000824416 (9:136950101 G>C), RS1001110918 (9:136950211 A>C,G,T), RS1001413138 (9:136950755 A>G,T), RS1001500089 (9:136947927 C>T), RS1001560100 (9:136956663 G>T), RS1001586424 (9:136952688 C>A,T), RS1001619532 (9:136956347 A>G), RS1001783762 (9:136948128 C>G,T), RS1001985879 (9:136955386 C>G,T), RS1002050337 (9:136956669 A>G), RS1002351545 (9:136954983 TACAC>T,TAC), RS1002383570 (9:136949203 G>A,T)

Disease associations

OMIM: gene MIM:612905 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
Tourette syndrome	No Known Disease Relationship	Unknown

Mondo (1): Tourette syndrome (MONDO:0007661)

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001806_14	Corneal structure	6.000000e-12
GCST005667_19	Central corneal thickness	5.000000e-17
GCST009414_34	Central corneal thickness	8.000000e-15
GCST90000654_29	Central corneal thickness	3.000000e-16
GCST90013442_14	Keratoconus	1.000000e-11

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004345	corneal topography
EFO:0005213	central corneal thickness

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D005879	Tourette Syndrome	C10.228.140.079.898; C10.228.662.825.800; C10.574.500.850; C16.320.400.820; F03.625.992.850

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, decreases expression, increases abundance, increases expression	4
Benzo(a)pyrene	decreases expression, increases expression	2
Tetrachlorodibenzodioxin	increases expression	2
methyleugenol	decreases expression	1
pirinixic acid	increases activity, affects binding, decreases expression	1
gallium arsenide	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
Air Pollutants	increases expression, increases abundance	1
Arsenic	increases abundance, increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
N-Nitrosopyrrolidine	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	increases methylation	1
Cyclosporine	decreases expression	1
Okadaic Acid	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00152750	PHASE4	UNKNOWN	Study of Clonidine on Sleep Architecture in Children With Tourette’s Syndrome (TS) and Comorbid ADHD
NCT00226824	PHASE4	TERMINATED	Safety Study of Galantamine in Tic Disorders
NCT00241176	PHASE4	COMPLETED	Open Label Trial of Aripiprazole in Children and Adolescents With Tourette’s Disorder
NCT00370838	PHASE4	COMPLETED	Comparison of Keppra and Clonidine in the Treatment of Tics
NCT01018056	PHASE4	COMPLETED	Developing New Treatments for Tourette Syndrome: Therapeutic Trials With Modulators of Glutamatergic Neurotransmission
NCT01547000	PHASE4	COMPLETED	Guanfacine in Children With Tic Disorders
NCT03239210	PHASE4	COMPLETED	Effects of Ondansetron in Obsessive-compulsive and Tic Disorders
NCT00004376	PHASE3	COMPLETED	Phase III Randomized, Double-Blind, Placebo-Controlled Study of Guanfacine for Tourette Syndrome and Attention Deficit Hyperactivity Disorder
NCT00206323	PHASE3	COMPLETED	A Randomized, Placebo-controlled, Tourette Syndrome Study.
NCT00206336	PHASE3	COMPLETED	An Open-label Study to Determine the Efficacy and Safety of Topiramate in the Treatment of Tourette Syndrome.
NCT00478842	PHASE3	COMPLETED	Pallidal Stimulation and Gilles de la Tourette Syndrome
NCT00681863	PHASE3	TERMINATED	Open-label Extension Study of Pramipexole in the Treatment of Children and Adolescents With Tourette Syndrome
NCT01501695	PHASE3	COMPLETED	Phase III Study of 5LGr to Treat Tic Disorder
NCT03087201	PHASE3	COMPLETED	CANNAbinoids in the Treatment of TICS (CANNA-TICS)
NCT03487783	PHASE3	COMPLETED	Aripiprazole Oral Solution in the Treatment of Children and Adolescents With Tourette’s Syndrome
NCT03567291	PHASE3	TERMINATED	Evaluation of Safety and Tolerability of Long-term TEV-50717 (Deutetrabenazine) for Treatment of Tourette Syndrome in Children and Adolescents
NCT03571256	PHASE3	COMPLETED	A Study to Test if TEV-50717 is Effective in Relieving Tics Associated With Tourette Syndrome (TS)
NCT06021522	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate Long-term Safety of Ecopipam Tablets in Children, Adolescents and Adults With Tourette’s Disorder
NCT00004393	PHASE2	COMPLETED	Phase II Double Blind Placebo Controlled Trial of Risperidone in Tourette Syndrome
NCT00004652	PHASE2	COMPLETED	Phase II Pilot Controlled Study of Short Vs Longer Term Pimozide (Orap) Therapy in Tourette Syndrome
NCT00231985	PHASE2	COMPLETED	Effectiveness of Behavior Therapy and Psychosocial Therapy for the Treatment of Tourette Syndrome and Chronic Tic Disorder
NCT00311909	PHASE2	COMPLETED	Thalamic Deep Brain Stimulation for Tourette Syndrome
NCT00529308	PHASE2	COMPLETED	Transcranial Magnetic Stimulation (TMS) for Individuals With Tourette’s Syndrome
NCT00558467	PHASE2	COMPLETED	Pramipexole Pilot Phase II Study in Children and Adolescents With Tourette Disorder According to DSM-IV Criteria
NCT01043549	PHASE2	TERMINATED	Repetitive Transcranial Magnetic Stimulation of the Posterior Parietal Cortex in Patients Suffering From Gilles de la Tourette Syndrome
NCT01133353	PHASE2	WITHDRAWN	A Study of the Effectiveness and Safety of Tetrabenazine MR in Pediatric Subjects With Tourette’s Syndrome
NCT01475383	PHASE2	WITHDRAWN	Study Evaluating The Safety And Efficacy Of PF-03654746 In Adult Subjects With Tourette’s Syndrome
NCT01647269	PHASE2	COMPLETED	A Trial of Bilateral Deep Brain Stimulation to the Globus Pallidus Internum in Tourette Syndrome
NCT01904773	PHASE2	COMPLETED	Safety, Tolerability, Pharmacokinetic, and Efficacy Study of AZD5213 in Adolescents With Tourette’s Disorder
NCT02102698	PHASE2	COMPLETED	Ecopipam Treatment of Tourette’s Syndrome in Subjects 7-17 Years
NCT02217007	PHASE2	WITHDRAWN	A Trial Evaluating the Efficacy, Safety, and Pharmacokinetics of SNC-102 in Subjects With Tourette Syndrome
NCT02247206	PHASE2	COMPLETED	VoIP Delivered Behavior Therapy for Tourette Syndrome
NCT02581865	PHASE2	COMPLETED	Safety and Efficacy Study of NBI-98854 in Adults With Tourette Syndrome
NCT02619084	PHASE2	COMPLETED	Subthalamic Stimulation in Tourette’s Syndrome
NCT02679079	PHASE2	COMPLETED	Safety and Efficacy Study of NBI-98854 in Children and Adolescents With Tourette Syndrome
NCT02879578	PHASE2	COMPLETED	Safety and Tolerability Study of NBI-98854 for the Treatment of Subjects With Tourette Syndrome
NCT03066193	PHASE2	COMPLETED	Efficacy of a Therapeutic Combination of Dronabinol and PEA for Tourette Syndrome
NCT03247244	PHASE2	TERMINATED	Safety and Efficacy of Cannabis in Tourette Syndrome
NCT03325010	PHASE2	COMPLETED	Safety, Tolerability, and Efficacy of NBI-98854 for the Treatment of Pediatric Subjects With Tourette Syndrome
NCT03444038	PHASE2	COMPLETED	Open-Label Safety and Tolerability Study of NBI-98854 for the Treatment of Pediatric Subjects With Tourette Syndrome